# T cell therapy targeting multiple tumor antigens in lymphoma

> **NIH NIH P50** · BAYLOR COLLEGE OF MEDICINE · 2021 · $264,591

## Abstract

Project Summary/Abstract
Project 1 proceeds from its demonstration during the last funding cycle that T cells targeting 5 tumor-expressed
antigens (PRAME, SSX2, MAGEA4, NY-ESO-1, and Survivin - multiTAA T cells) can be used to effectively treat
relapsed/refractory Hodgkin and non-Hodgkin lymphoma. Indeed, 5 of 9 patients with active disease achieved
durable compete remissions when infused with multiTAA T cells, an outcome that correlated with the detection
of tumor-reactive T cells in peripheral blood. This renewal proposal is designed to improve on these results by
addressing two remaining barriers to successful cancer immunotherapy: (a) immune escape due to low target
antigen expression and (b) the hostile tumor microenvironment, which can subvert the effector function and limit
the persistence of infused T cells. To enhance target antigen expression on malignant cells, we will precondition
patients with a DNA hypomethylating agent, 5-azacytidine, that upregulates tumor-associated antigens (TAAs)
and then relate the biological effects of treatment to subsequent clinical responses (Aims 1 and 2). We predict
that the increased target antigen expression on malignant cells will enhance their killing by the adoptively
transferred T cells and lead to more effective recruitment and activation of endogenous cellular immune
responses, resulting in epitope spreading that will potentiate the antitumor effects of the multiTAA T cells and
thus the clinical benefit to patients. In addition, to convert the hostile tumor milieu into one that promotes rather
than inhibits T-cell function, we will engineer our multiTAA T cells to express customized inverted cytokine
receptors (ICRs) designed to interact with immunosuppressive tumor-derived molecules (TGFꞵ and IL4) but
deliver costimulatory and cytokine signals (4-1BB and IL7) that promote rather than inhibit T cell proliferation,
activation, persistence and cytolytic activity (Aim 3). We predict that further benefit will derive from the
sequestration of these suppressive tumor molecules, which would otherwise support tumor growth and survival
while also polarizing the local environment towards inhibitory and tolerizing (Th2, Treg). Overall, we believe that
these modifications will enable the wide introduction of a genuinely transformative cellular therapy for the
treatment of relapsed/refractory lymphoma. This gain would not necessarily be limited to lymphoma; rather, the
flexibility of the therapeutic strategy should enable the antigenic specificity of the engineered T cells to be tailored
to each type of cancer under study.

## Key facts

- **NIH application ID:** 10247738
- **Project number:** 5P50CA126752-15
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Ann M. Leen
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $264,591
- **Award type:** 5
- **Project period:** 2007-04-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247738

## Citation

> US National Institutes of Health, RePORTER application 10247738, T cell therapy targeting multiple tumor antigens in lymphoma (5P50CA126752-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247738. Licensed CC0.

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