# Imaging Immune Modulation in Chimeric Antigen Receptor (CAR) T Cell Therapy

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $768,857

## Abstract

PROJECT SUMMARY
 
 Chimeric antigen receptor (CAR) T-cell therapy is an active basic research and clinical program at MSKCC,
involving treatment of acute and chronic lymphocyte leukemia (CD19 CAR-specific) and advanced metastatic
prostate cancer (PSMA CAR-specific) autologous T cells. The latter study includes monitoring T cell trafficking
and persistence with 124I-FIAU/18F-FIAU and PET imaging. Our proposal compliments these on-going studies
at MSKCC and explores the benefits of adding immune modulation to CAR-directed T cell therapy.
 Our primary objective is to validate reporter imaging systems that can be used to concurrently monitor CAR-
directed T cell tumor targeting, activation and persistence (constitutive Reporter 1) and T cell activation (NFAT-
inducible Reporter 2), plus tumor progression or regression (constitutive Reporter 3) in small animal models of
prostate cancer. We also propose to develop a novel transgenic mouse colony that is immune tolerant to
human PSMA and our multiple reporter systems (but otherwise retains normal immune function); this mouse
colony will host orthotopic syngeneic MycCap murine tumors. We will also study an established human
prostate (orthotopic) xenografts in NOD SCID mice.
 Our secondary objectives are related to addressing biological and therapeutic questions; namely, whether
immune modulation strategies can enhance adoptive CAR-directed T cell therapy. They include: a) whether
inhibition of the PD-1/PD-1L receptor “check-point”, or whether the inhibition of CXCR4/CXCL12 signaling, or
whether inhibition of TGFβ1 signaling results in improved PSMA CAR-directed T cell targeting, activation and
treatment response; b) whether combined inhibition of the above immune modulatory effectors results in a
synergistic improvement of PSMA CAR-directed T cell targeting, activation and treatment response. We
propose to use the reporter systems (Aim 1) and transgenic immune competent host animal (Aim 2) to verify
our hypotheses by real-time imaging in appropriate animal models.
 Our central theme and hypothesis are that: 1) concurrent imaging and monitoring of T cell tumor targeting,
activation and persistence, plus tumor progression (or regression) in small animal models of prostate cancer is
feasible; 2) T cell exclusion from the tumor mass occurs in both murine and human prostate cancer animal
models; 3) Immune modulation therapy (described above) will reverse T cell exclusion from the tumor and
result in improved PSMA CAR-directed T cell tumor targeting, activation and treatment response; 4)
Combined inhibition, using the above immune modulatory effectors, will result in a synergistic improvement of
PSMA CAR-directed T cell tumor targeting, activation and treatment response. It should also be noted that we
have compared several human PET-based reporter systems in transduced human T cells that would be
suitable for future clinical studies (the PET-based reporters are not part of this application).

## Key facts

- **NIH application ID:** 9966901
- **Project number:** 5R01CA204924-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Vladimir Ponomarev
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $768,857
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966901

## Citation

> US National Institutes of Health, RePORTER application 9966901, Imaging Immune Modulation in Chimeric Antigen Receptor (CAR) T Cell Therapy (5R01CA204924-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9966901. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*