# Engineering stem cell-derived T cells for immunotherapy

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $36,901

## Abstract

PROJECT SUMMARY/ABSTRACT
Adoptive cell transfer (ACT) immunotherapies repurpose T cells from patients to specifically eliminate tumor
cells by engineering them to express antigen-specific T cell receptors (TCRs) and chimeric antigen receptors
(CARs). Currently, engineered T cell manufacturing is patient-specific and the timeline and cost of manufacture
which may limit access to these new therapies. Some patients have a prognosis for survival that does not end
beyond the inherent time required for cell manufacturing (on average 22 days for a current FDA-approved CAR-
T product), and clinical responses are uneven and are related, at least partly, to the functional variability of the
T cell composition of each product. This proposal seeks to remove these barriers by engineering human
pluripotent stem cells (hPSCs) to generate non-alloreactive, antigen-specific mature, naïve T cells using the
Artificial Thymic Organoid (ATO) system, a novel in vitro method for efficiently and reproducibly producing
mature, naïve T cells from stem cell sources. CRISPR/Cas9 gene-editing will be used in hPSCs to generate
insertion deletion mutations (INDELs) to knockout the beta-2-microglublin (B2M) gene, the critical subunit of all
Class I MHC heterodimers, to prevent Class I MHC-mediated allo-rejection of T cells. To prevent the
rearrangement of endogenous, and potentially allo-reactive TCRs, a multiplex CRISPR/Cas9 strategy will be
used in hPSCs to completely excise the locus containing the recombination-activating-genes RAG1 and RAG2
in hPSCs. Together, these experiments will develop a platform for generating stem cell-derived, non-alloreactive
mature naïve T cells that could ultimately be applied toward an “off-the-shelf” approach to T cell immunotherapy.

## Key facts

- **NIH application ID:** 10104356
- **Project number:** 5F31CA239555-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Patrick C Chang
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,901
- **Award type:** 5
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104356

## Citation

> US National Institutes of Health, RePORTER application 10104356, Engineering stem cell-derived T cells for immunotherapy (5F31CA239555-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10104356. Licensed CC0.

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