Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) encourages grant applications to study novel microbial-based cancer therapy (including therapies for oral cancer), imaging detection, and diagnosis strategies to overcome the limitations of inadequate conventional cancer imaging and therapies. Solutions may utilize bacteria, archaebacteria, bacteriophages, and other microorganisms and their products (but not oncolytic viruses).

This NOFO utilizes the R01 mechanism and is suitable for projects studying the underlying mechanisms of the complex interactions between microorganisms and tumors and the immune system, their therapeutic use, their utilization as delivery vehicles for cancer treatment, and imaging to complement or synergize with current cancer therapy and imaging. This NOFO will accept basic, mechanistic, and/or more applied preclinical studies in cell culture, animal models, or in vivo tumors including oral cancer. The R01 mechanism is suitable for projects where supportive preliminary data are available.

This NOFO runs in parallel with an NOFO of identical scientific scope, PAR-25-108 , which uses the Exploratory/Developmental Grant (R21) mechanism.

Background and Rationale

Background and rationale Early clinical observations in the 1880s by Coley pioneered the concept of using bacteria (or their products) as microbial-based cancer therapy and demonstrated that tumor regression coincided with natural bacterial infections, leading to the first use of microbes as antitumor agents. With the development of the more effective and better-understood radiation therapy, and later, chemotherapy-based cancer therapies, this approach was largely abandoned in the 1930s and microbial-based therapy has remained an elusive goal. However, standard cancer therapies have several major disadvantages, including the rarity of complete and sustained remissions of most solid tumors, the development of resistance, frequent failure to clear micrometastases, and relapse. To overcome the limitations of current cancer imaging and therapies, microbial tumor homing and colonization, oncolysis, and activation of anti-tumor immunity are being explored as alternative strategies. Because Bugs as Drugs are potentially self-regenerated cancer therapeutics, the approach may address cancer therapy needs for global health and low resource settings

Mechanisms of Microbial-based Cancer Therapy

Several facultative or obligate anaerobic bacteria possess unique natural or genetically engineered potential to overcome traditional therapeutic limitations by selectively targeting tumors and/or anti-tumor immunity. For example, Salmonella, Escherichia coli, Clostridium, Bifidobacterium, or Listeria are naturally capable of selective homing to tumors when systemically administered, resulting in high levels of colonization and replication in locally hypoxic tumor microenvironments or within tumor tissues leading to killing tumor cells, reprograming the immune system to target cancer cells. Therapeutic bacteria can stimulate the production or localized in the tumor of CD8+T lymphocytes or block immune checkpoint pathways.

Microbial products (including microbial toxins) and microbial metabolites are also associated with anti-tumor activities. Microbial metabolites can inhibit tumor cells growth in vitro, modulate T-cell response to checkpoint inhibitors, reduce carcinogenic inflammation, inhibit tumor cell invasion and migration, suppress histone deacetylase activity, and induce apoptosis

Cancer Clinical Needs and Challenges

There is a need for improved cancer therapies (including therapies for oral cancer), especially for solid tumors where conventional therapies often fail under conditions such as poorly vascularized tumors with inadequate blood perfusion, hypoxia, nutritional deprivation, tumor interstitial pressure, immature lymphatic system, immunosuppressive microenvironment, tumor dormancy, distant tumor metastasis, slowly dividing cells resistant to treatment, or islands of microinvasive tumor cells buried within normal tissues and drug resistance. In addition, it is important to develop new cancer immunotherapy modalities. Among the most attractive characteristics of microbial agents for anticancer therapies is their capacity for tumor-specific targeting and activation of the immune system. Thus, for example, it may be possible to develop a bacteria-based cancer treatment platform for in situ release of immune checkpoint inhibitors.

Recent research advancements in bacterial anti-cancer activities

Multiple studies have demonstrated that anaerobic microorganisms have the unique ability to grow selectively in hypoxic immunosuppressed areas of solid tumors that often are not accessible to drugs. More recently, an integrated bacterial cancer treatment approach utilizing a single multi-function, bacterial payloads for cancer imaging, activation of the immune system, and tumor cell killing were demonstrated. A white paper on the Challenges and Opportunities of Microbial Anti-Cancer Therapy and Prevention summarizes the potential of microbial therapy and recent research advances. Promising results from these studies and the availability of sophisticated gene-editing technology, offer the prospect of developing new concepts and strategies for the use of microbial therapies to mitigate or solve unmet clinical needs. Other studies have shown that gut microbial metabolites can modify the transcription, epigenetics, and metabolism of host immune cells, which can be utilized to activate the immune system. While recent research demonstrates the potential of microbial-based cancer therapy, more research is needed to realize this potential and to bring novel microbial-based therapies to the clinic especially for conditions where conventional cancer therapies are inadequate

Scope and Research Objectives of this NOFO

The complex nature of the interactions between the microbe, tumor, and immune system requires multidisciplinary collaboration between microbiologists, cancer researchers, and immunologists with the goal of developing innovative approaches to improve our understanding of this system and utilize it for cancer therapy. This initiative seeks to support studies of tumor-microbe interactions needed to develop new cancer imaging and therapy strategies that address unmet clinical needs. The multi-disciplinary research teams are expected to conduct cutting-edge research aimed at advancing pre-clinical development of novel bacteria-based anticancer therapeutic or diagnostic agents. The goal is to conduct research that could have a major impact on cancer therapy and related research

Multi-disciplinary research teams are expected to conduct cutting-edge research within the scope of the NOFO(see above) aimed at advancing pre-clinical development of novel microbial-based anticancer therapeutic agents, cancer imaging, and diagnostics technologies, or to study the complex biology involved in the interplay of microbe-tumor-immune system interactions. Applicants applying to this NOFO are expected to address both the microbial and the tumor aspects of microbial cancer therapy, the goal is to conduct research that could have a major impact on cancer therapy and related research.

Potential areas of research may include, but are not limited to:

• The basic biology of the underlying microbe-tumor interactions such as invasion, lysis, antigen presentation, and other microbe-initiated tumor cell death;
• Microbial (or microbial products) interactions with the immune system, including microbial induction of specific antitumor immunity for primary and metastatic tumors, including immune engagement, more robust tumor antigen presentation, immunostimulatory constructs such as “trojan horse” delivery of novel antigen expressions to overcome immune suppression;
• Tumor cell inactivation (including colonization, disrupting cell function, activation of cell death programs, etc.);
• Novel microbial species that might have therapeutic/imaging potential e.g., soil, aquatic and plant, bacteria, archaebacteria, bacteriophages, and other non-oncolytic viruses as potential therapeutics to overcome the issues of microbial pathogenicity and clearance by the immune system;
• The dynamics of microbe-tumor interactions and biological factors limiting the effectiveness of microbial-based cancer therapy;
• The molecular mechanisms by which microbes and microbial products modulate cancer treatment responsiveness;
• Interaction between microbes or microbial products with the immune system to develop novel cancer immunotherapies;
• Novel microbial cancer-targeting approaches;
• Novel microbial anti-cancer products (including microbial toxins) and microbial metabolites;
• Integrated multi-function bacterial payload for cancer imaging and therapy;
• Microbial bioreactors for self-supplied tumor localized antitumor agents;
• Microbial based imaging for cancer detection and diagnosis
• Approaches for treating poorly vascularized hypoxic solid tumors or islands of microinvasive tumor cells buried within normal tissue;
• Approaches for treating distant tumor metastasis;
• Activation of anti-tumor immunity (including expressing foreign proteins on the surface of the tumor cell);
• Microbial based asymptomatic cancer detection;
• Activation of dormant tumor cells;
• Natural or engineered non-pathogenic microbes with therapeutic potential to selectively infect and treat cancers of various organs, solid tumors, metastasis, microinvasion, hypoxic or poorly vascularized tissues not accessible to chemical or monoclonal antibody drugs;
• Targeting specificity for primary and metastatic tumors, hypoxic tissues, poorly vascularized tissues, neovascularization, or slowly dividing/dormant cancer cells;
• Novel microbial drug delivery approaches and microbial payload delivery of anti-cancer drugs, imaging agents, radiotherapy, other tumor-relevant payloads;
• Long-lasting approaches to anti-cancer immunity, such as the surface expression of foreign proteins to induce a strong response or overcome immune suppression;
• Tumor cell inactivation, such as colonization, cell function disruption, programmed cell death activation;
• Approaches to balance among microbe-initiated immune stimulation, cancer neoantigen presentation, therapeutic microbes clearance, and microbial pathogenicity for more nearly optimal safety and efficacy of microbial-based anti-cancer agents; and
• Strategies to prevent a recurrence, such as prolonging microbial therapy efficacy with libraries of “foreign” antigens to restimulate the immune system after loss of initial antigen efficacy.

Microbial-based Cancer Detection and Diagnosis

Microbial species with cancer-selective homing to tumors and colonization have the potential to overcome traditional cancer detection and diagnosis limitations, especially for asymptomatic cancers. Microbes are potentially useful for tumor detection and diagnosis and may provide information about the tumor organ site and characteristics, which facilitates cancer staging, management, and treatment

Microbial-based Cancer Detection and Diagnosis Specific Research Areas:

• Enhancing bacterial tumor colonization for cancer detection and diagnosis applications;
• Analysis of microbial-cancer specific organ targeting for cancer detection and diagnosis;
• Microbial-based cancer diagnosis/detection technologies (including blood microbial “biomarkers”, DNA, metabolite, or other microbial characteristics;
• Manipulation of the microbial tumor population to improve cancer therapy;
• Microbial labeling for microbial-based cancer imaging detection;
• Microbial-based cancer distant tumor metastasis detection; and
• Microbial-based detection of asymptomatic cancers.

Microbial-based Cancer Imaging

Many facultative or obligate anaerobic bacteria and engineered bacteria are capable of selective homing and penetrating tumors when systemically administered which is potentially useful for tumor in vivo imaging. By using tumor-specific colonization properties of labeled bacteria, it may be possible to enhance the resolution and sensitivity of various in vivo tumor imaging modalities including CT, MRI, PET, SPECT, ultrasound, optical imaging, etc. for tumor margin detection/excision.

Cancer Imaging Specific Research Areas:

• Enhancing bacterial tumor colonization and penetration for imaging applications;
• Microbial-specific contrast agents and molecular imaging probes for the various in vivo imaging modalities;
• Microbial labeling for microbial-based cancer detection;
• Developing precise spatiotemporal resolution (including computation and image manipulation) of microbial-based cancer imaging;
• Microbial-based image-guided tumor margin detection/accurate excision;
• Microbial-based cancer distant tumor metastasis imaging; and
• Microbial-based image-guided drug, gene, or radiation therapy in vivo.

Researchers who emphasize on applying cancer imaging technologies for assessing in vivo changes occurred in the local tumor microenvironment or tumor-induced systemic environment as the result of microbial based intervention should consider applying to PAR-24-311, Molecular Imaging of Inflammation in Cancer (R01 Clinical Trial Not Allowed).

NCI's Center for Global Health

Microbial-based cancer therapy may provide new opportunities, because of the relative simplicity of microbial culturing, microbes may have the potential to be self-regenerating cancer therapeutics, the ultimate sustainable cancer treatment for Low and Low Middle Income Countries (LMIC).

LMIC. Examples of the Center for Global Health specific topics of interest may include:

• Low-cost microbial-based cancer therapies and diagnosis for low resource settings;
• Novel cancer-targeting approaches suitable for LMICs; and
• Microbial cancer therapy delivery approaches suitable to LMICs.

National Institute of Dental and Craniofacial Research (NIDCR)

NIDCR support for this initiative includes research and development of bacterial anticancer agents for the treatment of cancers of the oral cavity, oropharynx, and salivary glands. Therefore, in addition to the general areas of research listed above, examples of NIDCR-specific topics include:

• Microbial-based treatment of oral, salivary gland, or oropharyngeal cancers;
• Microbial delivery of anti-cancer therapeutics to oral, salivary gland, or oropharyngeal tissues;
• Microbial manipulation of the oral microbiome to reduce the risk of developing cancers of the oral cavity, oropharynx, and salivary gland;
• Microbial or microbial metabolite-based inhibition of HPV acquisition, infection, and persistence in the oral cavity to prevent oral cancers; and
• Microbial-based cancer imaging and applications solely focused on “microbial community-level analysis” will be considered non-responsive for NIDCR.

Team Structure

Through this NOFO, NCI encourages the formation of multi-disciplinary teams with expertise in microbiology, immunology, and molecular/cellular cancer biology from diverse academic, clinical, or industrial sources to ensure breadth sufficient to accomplish project goals. Each application should address how all project elements are represented, assignment of project modules, and performance targets for completion of all steps.

Non-responsive Applications

Applications that propose the following will be deemed non-responsive to mission of this NOFO and will not be reviewed: 

• Research on oncolytic viruses (for NCI); and
• Microbial-based cancer imaging and applications solely focused on “microbial community-level analysis” (for NIDCR).

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized).

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Avi Rasooly, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6196
Email: [email protected]

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Specific Aims: Include a brief sub-section "Statement of Potential Impact" describing the expected potential of the proposed approach to transform cancer therapy and clinical practice. The following questions should be addressed with this statement.

• How the new approach provided by the proposed research is potentially transformative and why may it be expected to have a high impact on cancer therapy (i.e., describe the potentially transformative outcomes that might be realized should this approach succeed).
• If applicable, describe how will the proposed approach overcome limitations for currently available therapies or alternative approaches? (i.e., provide evidence to support the claim of effectiveness beyond currently available therapies).

Research Strategy: The Research Strategy should clearly describe or address the following:

• Rationale for choice of comparison groups to assess differences in microbial changes as a function of cancer-related treatment, imaging or diagnosis.
• Clear justifications for the inclusion of specific cancer treatment regimens (chemotherapy, hormonal and/or molecular targeted therapies) in the research protocol.
• Clear justifications for the choice of microrganism used, cancer site, cancer stage, microbial assessment approach and schedule for assessments.
• Sound recruitment strategies to obtain a broad range of microbial ability via outreach/recruitment to understudied and demographically diverse samples (e.g., low socioeconomic status or educational attainment, rural, and race/ethnicity).
• Potential impact of the approach for conditions where conventional cancer therapies are inadequate, such as metastatic tumors, poorly vascularized, hypoxic, solid tumors, dormant or slowly dividing cells resistant to current interventions, islands of microinvasive tumor cells buried within normal tissues and brain tumors.
• If a preclinical animal model research project is proposed, then include:
  • Description of the translational relevance of the model and the microbial treatment science paradigms being used.
  • Justification of the translational relevance of the use of tumor-bearing or tumor naïve animal models.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will evaluate Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate criterion score. 

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR) , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Not Applicable

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Avi Rasooly, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6196
Email: [email protected]
(Cancer Therapy Applications)

Phil Daschner Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6227
Email: [email protected]
(Cancer biology and basic research)

Luis Alejandro Salicrup, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5799
Email: [email protected]
(Global Health)

Miguel Ossandon, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5714
Email: [email protected]
(Microbial Based Cancer Diagnostics)

Yisong Wang, Ph.D.
National Cancer Institute (NCI)
Telephone: [email protected]
Email:240-620-0690
(Microbial based Cancer Imaging)

Zhong Chen, M.D., Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-7083
Email: [email protected]

Zhong Chen, MD, PhD
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 3015297083
E-mail: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
E-mail: [email protected]

Diana Rutberg, MBA
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: [email protected]

Gabriel Hidalgo, MBA
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-827-4630
E-mail: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.