# CAR T cell therapy for T cell lymphoma

> **NIH NIH P50** · BAYLOR COLLEGE OF MEDICINE · 2020 · $299,192

## Abstract

PROJECT SUMMARY
Patients with primary refractory or relapsed T-cell lymphoma typically have a poor prognosis and limited
options for effective targeted therapy. This contrasts with the clinical success of using CD19-specific chimeric
antigen receptors (CARs) in immunotherapies for B-cell malignancies. Thus, to begin to achieve the long-
term goal of devising a CAR-T cell platform that can be safely and effectively applied in patients with T-cell
lymphoma, new Project 2 has selected CD5 as a novel target antigen for CAR-transduced cells. This
common surface marker of normal T cells is also expressed by an estimated 85% of T-cell malignancies and
functions as a transmembrane inhibitory receptor that attenuates signaling from the antigen receptor of T cells
and a subset of B cells. Importantly, CD5-specific CAR-T cell fratricide (self-killing) is limited in our
experimental model, allowing the CAR-modified cells to expand normally, after which they display potent and
selective cytotoxicity against malignant T cells. Nonetheless, we reasoned that a second target antigen might
be helpful, as antigen loss during treatment is a major obstacle to truly successful therapy, in patients receiving
CD19-specific CAR-T cells, for example. CD7 was judged the best candidate as it is expressed at a high level
on >90% of T-lymphoblastic lymphomas and >60% of mature lymphomas including those lacking CD5.
Although in preliminary studies CD7-specific CARs showed strong activity against CD7+ target cells, the
transduced T cells did not rapidly downregulate CD7, leading to enhanced fratricide that abrogated further
expansion. This pitfall was eliminated by targeted depletion of the antigen in the CAR-modified T cells, a step
that did not compromise either expansion or antitumor activity. Given these positive findings, we hypothesize
that CD5-specific CAR-T cells can be safely used to target CD5+ T-cell lymphomas and induce complete
remissions, and that CD7- cells will continue to expand and function in even in the presence of CD7-directed
CARs by T cells. We propose to test each strategy in the following specific aims.
Aim 1: Manufacture the GMP-grade vector and develop the SOPs needed for a clinical trial of CD5-specific
CAR-T cells in T-cell lymphoma, and obtain all necessary local and federal regulatory approval.
Aim 2: Conduct and evaluate a clinical trial using CD5 CAR-T cells to induce remissions in individuals with
residual T-cell lymphoma who would then become eligible for allogeneic stem cell transplant.
Aim 3: Express the CD7-specific CAR on CD7- effector T cells as a means to increase the range of targetable
tumors and overcome CD5 antigen escape.
Our proposed studies of CD5-specific CARs and the preclinical development of a CD7-specific CAR will do
much to substantiate and advance our CAR-based platform for the treatment of T-cell malignancies and would
provide a scientific basis for further optimization.

## Key facts

- **NIH application ID:** 10000867
- **Project number:** 5P50CA126752-14
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** MALCOLM K. BRENNER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,192
- **Award type:** 5
- **Project period:** 2007-04-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000867

## Citation

> US National Institutes of Health, RePORTER application 10000867, CAR T cell therapy for T cell lymphoma (5P50CA126752-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10000867. Licensed CC0.

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