# Adoptive T Cell Therapy for Pancreatic Cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $613,867

## Abstract

Pancreatic cancer will be responsible for over 44,000 deaths in the US this year and is currently the 3rd
leading cause of cancer mortality; survival in this disease has not changed in the last 40 years. Although
immune checkpoint inhibitors have emerged as highly effective approaches for tumors with high
mutational burden, such is not the case with pancreatic cancer which lacks a significant endogenous
tumor-reactive T cell population. Adoptively transfer of antigen-specific T cells would provide an effector
substrate for immune checkpoint inhibition and we reason that such a combination strategy would be
desirable. In this proposal we address two major challenges to advancing the use of adoptive cellular
therapy (ACT) for pancreatic cancers: 1. a paucity of proven immunogenic targets for pancreatic cancer
and, 2., a means of rapidly deploying antigen-specific cellular therapy targeting such antigens. In this
proposal we plan to target a tumor cell-associated target antigen (VCY) and a tumor stroma-associated
target (COL6A3), both highly prevalent (> 70% of tumors), and highly immunogenic. Our scientific
premise is that strategies that address the lack of tumor-reactive T cells in pancreatic cancer, where the
mutational burden and immunogenicity is significantly lower, would be desirable and achievable by the
adoptive transfer of tumor-reactive T cells recognizing pancreatic cancer-associated antigens.
Adoptive cellular therapy (ACT) is a promising form of immunotherapy that involves the ex vivo isolation
and expansion of antigen-specific T cells for infusion. Based on the premise that strategies to extend
in vivo persistence of transferred T cells and induce antigen-spreading will lead to improved
clinical response following ACT, we hypothesize that adoptive transfer of long-lasting central memory
type T cells in combination with PD1 blockade will lead to extended in vivo survival and enhanced
activation of endogenous T cells recognizing non-targeted antigens (antigen-spreading).
Our ETC (endogenous T cell therapy) approach to ACT was to pioneer a strategy that uses peripheral
blood as a source of T cells. Using a combination of IL-21 priming (to enrich for central memory type T
cells) and tetramer-guided cell sorting, we can routinely isolate rare tumor-reactive T cells from the
peripheral blood ( < 1:100,000) and expand these to a > 20 billion uniformly defined central memory –
type specific T cells with defined specificity and high replicative capacity as demonstrated by several
prior studies demonstrating months-long in vivo persistence at frequencies 1-10 % commensurate with
durable clinical responses. We propose a Phase IB trial targeting COL6A3 and VCY in patients with
refractory pancreatic adenocarcinoma, first in a dose escalation cohort, and when a dose has been
identified, an expansion cohort in combination with PD1 blockade.

## Key facts

- **NIH application ID:** 10456733
- **Project number:** 5R01CA237672-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Cassian Yee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $613,867
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456733

## Citation

> US National Institutes of Health, RePORTER application 10456733, Adoptive T Cell Therapy for Pancreatic Cancer (5R01CA237672-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10456733. Licensed CC0.

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