# Functional T cells from iPSCs Using Chimeric Antigen Receptors

> **NIH NIH F32** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $73,650

## Abstract

Project Summary:
T cell immunotherapy is poised to be a major player in the future of medicine. The success of CD19 CAR T
cells in acute lymphoblastic leukemia has been impressive and gives a glimpse of what the next generation of
engineered T cells may be capable of. In the future, CAR-targeted T cells may be valuable immunotherapy for
more than just cancer. In particular, targeted T regulatory cell therapy is a promising possibility for treatment of
autoimmune conditions and tolerance induction in transplant recipients. Current methods of CAR T cell
production are dependent on laborious isolation, modification, and expansion steps on a per-patient basis.
This makes them highly expensive with little possibility of an off-the-shelf product. Induced pluripotent stem
cells (iPSC) allow the reprogramming of adult somatic cells to a stem-cell like fate from patients with specific
MHC haplotypes to overcome this issue. The combination of MHC-banked iPSCs and CAR technology sets
the stage for a renewable and highly controllable off-the-shelf T cell therapeutic. However, efforts to
differentiate iPSCs into T cells have struggled with the production of hematopoietic progenitors with robust T
cell potential and a blockade in T cell maturation at the CD4/8 double positive stage. In this proposal we
demonstrate the marked impact of modulating the NOTCH signaling pathway on T-capable progenitor output.
We propose to combine this success with single-cell RNAseq to reveal the true identity of the T cell progenitor.
This work will uncover key signaling pathways and answer lingering questions about the nature of iPSC-
derived hematopoietic progenitors. It will also leverage improved efficiency in differentiation cultures. In
addition, we propose to use temporally controlled expression of CARs with a range of antigen affinities during
T cell differentiation to bypass their developmental blockade and drive maturation into functional T cells.
These two synergistic but not dependent goals will be a vital and powerful step toward truly functional iPSC-
derived T cells and would also open the door for exploring signals necessary to drive CD4 helper T cell
commitment and T reg lineage specification.

## Key facts

- **NIH application ID:** 9970164
- **Project number:** 5F32HL149605-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Dar Heinze
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $73,650
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970164

## Citation

> US National Institutes of Health, RePORTER application 9970164, Functional T cells from iPSCs Using Chimeric Antigen Receptors (5F32HL149605-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970164. Licensed CC0.

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