# Integration of neo-antigen vaccines and immune checkpoint therapy

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2021 · $391,107

## Abstract

Project 1 Summary
Immune-checkpoint inhibitors (ICIs) are providing durable clinical responses in about 20% of cancer patients,
but have minimal effect in cancers lacking intra-tumoral T cells. Approaches that turn T cell deplete cancers into
ones that attract high quality T cells are needed to sensitize these unresponsive cancers to ICIs. Most tumors
have somatic mutations that encode for mutant proteins that are tumor–specific and not expressed on normal
cells (termed neoantigens). Cancers with the highest mutational burdens are more likely to respond to single
agent ICIs. However, most cancers, including pancreatic adenocarcinoma (PDA) have lower mutational loads,
resulting in lower antigenicity, weaker endogenous T cell repertoires, and fewer T cells infiltrating the tumor.
PDAs also have an immunosuppressive tumor microenvironment (TME) consisting of suppressive monocytes,
B cells and T cells that express T cell inhibitory signals and exclude T cells or suppress them within the TME.
However, we published data showing in genetically–engineered KPC mice expressing the oncoprotein mutated
KRAS (mKRAS), that premalignant lesions can be prevented from progressing to PDA when a mKRAS vaccine
is given with ICIs. More recently, we published in the murine Panc02 model that expresses about 50 neoantigens
similar to human PDA, that a neoantigen targeted peptide vaccine (PancVAX) consisting of a mixture of 12
peptides each 20 amino acids long emulsed in adjuvant and given with ICIs, can treat PancO2 tumor-bearing
mice. Thus, in this proposal we will test the hypothesis that peptide vaccines targeting shared (mKRAS) or
personalized neoantigens will trigger high quality neoantigen–specific effector and effector memory T cells, which
will become available for further activation by ICIs and result in tumor rejection. We will conduct two human
clinical trials (Aims 1 and 2) to test vaccines targeting mKRAS and patient–tumor–specific neoantigens in
combination with ipilimumab and nivolumab in patients with resected and metastatic PDA, respectively. Moving
from the bedside back to the bench, in Aim 3, we will further develop our novel approaches arising from our
current data to enhance the immunogenicity of the neoantigen vaccines. Our new preliminary data has shown
that the inclusion of MHC Class II epitopes enhances CD8+ T cell response of our murine vaccine PancVAX
(which is composed primarily of MHC Class I epitopes). We will also interrogate the otherwise
immunosuppressive TME with targeted therapies that would potentially reprogram tumor-associated
macrophages and stromal cells in collaboration with Projects 3 and 4. In all instances, we will assess the quality
of T cells induced by each vaccine approach in combination with immune–modulatory agents. These studies will
inform future combination immunotherapy approaches for testing in Project 3 patients with PDA.

## Key facts

- **NIH application ID:** 10170020
- **Project number:** 1P01CA247886-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ELIZABETH M. JAFFEE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,107
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170020

## Citation

> US National Institutes of Health, RePORTER application 10170020, Integration of neo-antigen vaccines and immune checkpoint therapy (1P01CA247886-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10170020. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*