Development of novel neoantigen-based spherical nucleic acid immunotherapeutics
About This Grant
PROJECT SUMMARY Triple negative breast cancer (TNBC) is a highly invasive form of breast cancer with a dismal outcome, accounting for a staggering 25% of all breast cancer associated deaths despite comprising only 10-15% of cases. The standard of care for TNBC includes aggressive surgery, followed by radiation therapy and continued chemoimmunotherapy yet often results in a high rate of recurrence, formation of tumor resistance mechanisms, and metastasis, leading to poor patient outcomes. Current therapies are limited due to the lack of clear molecular targets, genomic instability, and the suppressive tumor microenvironment. Thus, there is an overwhelming need for targeted, effective, and safe therapeutics to combat TNBC. Flashpoint Therapeutics and the Gillanders Laboratory at Washington University School of Medicine (WUSM) proposed solution leverages the combined expertise of both teams to develop a targeted, personalized neoantigen cancer immunotherapeutic for TNBC using a structural nanomedicine platform. Cancer neoantigens represent a potentially optimal target to combat cancer as tumor-specific mutations can be utilized to selectively prime a specific immune response to target and destroy cancer cells while sparing healthy tissue. Additionally, delivery of RNA through lipid nanoparticles (LNPs) decorated with immunostimulatory spherical nucleic acids (SNA) has shown drastic improvement over conventional approaches. Having already demonstrated proof-of-concept feasibility for the safety and efficacy of TNBC personalized neoantigens and proven immunostimulatory RNA LNP SNA properties, we are poised to develop a patient-specific neoantigen-based personalized nanoparticle immunotherapeutic (PNI), termed P-SNA, for TNBC patients. In this Academic-Industrial Partnership R01 application we first aim to evaluate the efficacy and mechanism of action of our lead P-SNA candidate through in vivo preclinical breast cancer mouse models (Aim 1.1), and by use of fluorescently labeled constructs to determine biodistribution, immune activation, and immune priming (Aim 1.2). We will then chemically optimize our lead candidate to improve therapeutic properties using a rigorous Design of Experiments approach (Aim 2.1) and test the efficacy and mechanism of action of optimized candidates in vivo (Aim 2.2). As there is no model which can accurately or completely reproduce the complex immune and non-immune interactions that occur between the host and a tumor, even in the absence of vaccination, the only way to understand the impact of the P-SNA therapeutics are to test in well characterized animal models. Finally, we will develop GMP manufacturing protocols for the production of our optimized P-SNA lead GMP-compliant facilities (Aim 3.1) and complete FDA recommended IND-enabling studies (Aim 3.2). Together, these steps will enable the delivery of a lead P-SNA therapeutic for TNBC, fully characterized and optimized for efficacy and ready for clinical evaluation. Additionally, this work will establish a versatile platform for the development of P-SNAs for other cancer subtypes, increase our knowledge of immune mechanisms to fight cancer, and elucidate important aspects critical for rational PNI design and development.
Grant Summary
Development of novel neoantigen-based spherical nucleic acid immunotherapeutics is a NCI - National Cancer Institute grant providing up to $563K for university, nonprofit, healthcare org. Applications are due 2031-07-01 (open). Check eligibility and apply with FindGrants.
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Up to $563K
2031-07-01
- 1Confirm your organization is eligible for Development of novel neoantigen-based spherical nucleic acid immunotherapeutics from NCI - National Cancer Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCI - National Cancer Institute before the deadline.
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Development of novel neoantigen-based spherical nucleic acid immunotherapeutics: Frequently Asked Questions
Who is eligible for the Development of novel neoantigen-based spherical nucleic acid immunotherapeutics?
Development of novel neoantigen-based spherical nucleic acid immunotherapeutics is offered by NCI - National Cancer Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Development of novel neoantigen-based spherical nucleic acid immunotherapeutics provide?
Development of novel neoantigen-based spherical nucleic acid immunotherapeutics provides up to $563K per award from NCI - National Cancer Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Development of novel neoantigen-based spherical nucleic acid immunotherapeutics deadline?
Applications for Development of novel neoantigen-based spherical nucleic acid immunotherapeutics are due 2031-07-01 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Development of novel neoantigen-based spherical nucleic acid immunotherapeutics?
To apply for Development of novel neoantigen-based spherical nucleic acid immunotherapeutics, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCI - National Cancer Institute.