# Project 4 :Using TME genetics and immunobiology to drive combination immunotherapies

> **NIH NIH P50** · JOHNS HOPKINS UNIVERSITY · 2021 · $402,156

## Abstract

Abstract
Immunotherapy has become a game changer for about 20% of patients with metastatic cancers who
until now would die quickly of their disease. This new class of immunotherapies induce durable
responses that can last for years without further therapy. These agents (immune checkpoint inhibitors)
act on T cells that are inactivated due to immune checkpoint signals that inhibit their infiltration into and
function within tumors. But for about 80% of patients, immunotherapy has not been effective, and
immune unresponsiveness is likely the result of failure to activate effector T cells together with the
existence of multiple suppressive signals rather than a predominant immune checkpoint signal within
resistant tumors. Accumulating data suggests that it is possible to convert non-immunogenic tumors
into one that respond to immunotherapy. Thus, this proposal will address the next big question in
cancer immunotherapy: why do some cancers respond to checkpoint immunotherapy and exhibit
durable responses, while others either develop resistance (adaptive resistance) or are naturally
resistant. Understanding primary and adaptive resistance mechanisms will translate into effective
scientifically driven combination immunotherapies that combat resistance.
Our group has led the development of both single agent and combination therapy for pancreatic
adenocarcionoma (PDA) and colorectal carcinoma (CRC) and have recently received FDA
approval for Pembrolizumab for the treatment of patients with microsatellite instability (MSI)
high tumors. In addition, we have shown that treatment of patients with a vaccine can induce cancer
specific T cells that infiltrate into PDA and CRC tumors, opening the door for novel combination
immunotherapies. In this proposal, we will use specimens already collected and prospectively being
collected on trials that are demonstrating both sensitivity and primary and adaptive resistance to
immunotherapies, to define additional signals required to convert insensitive tumors into ones that
respond to immunotherapy.

## Key facts

- **NIH application ID:** 10246371
- **Project number:** 5P50CA062924-27
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ELIZABETH M. JAFFEE
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $402,156
- **Award type:** 5
- **Project period:** 1997-02-28 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246371

## Citation

> US National Institutes of Health, RePORTER application 10246371, Project 4 :Using TME genetics and immunobiology to drive combination immunotherapies (5P50CA062924-27). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10246371. Licensed CC0.

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