# Project 3: Developing CAR T Cell Therapies to Target Tumor Heterogeneity in Advanced Prostate Cancer

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $336,009

## Abstract

Developing CAR T Cell Therapies to Target Tumor Heterogeneity in Advanced Prostate Cancer
Therapies that inhibit androgen biosynthesis and target the androgen receptor are the mainstay of treatment for
patients with advanced prostate cancer. However, most men will eventually develop resistant disease that is
called castration-resistant prostate cancer (CRPC). Metastatic CRPC is not curable and treatments at this stage
are aimed at extending and improving quality of life. CRPC is a heterogeneous disease composed of at least
two subtypes including prostate adenocarcinoma and neuroendocrine prostate cancer (NEPC). Both CRPC
subtypes are found together in many lethal, treatment-resistant prostate cancers. New and potent therapies that
account for and eliminate the heterogeneity of CRPC are urgently needed.
Chimeric antigen receptor (CAR) T cell therapy is a revolutionary advance in oncology that combines precision
targeting with powerful killing of tumor cells. In this approach, a patient’s own immune T cells are collected from
the blood, genetically engineered to recognize and kill his/her specific cancer and reintroduced into the patient.
This technology has the potential to transform the treatment of cancer including those that have been considered
incurable. Our group has pushed forward the first CAR T cell therapy for metastatic CRPC to a clinical trial by
building on a series of scientific accomplishments. We discovered that prostate stem cell antigen (PSCA) is a
protein expressed on the surface of the majority of prostate adenocarcinomas, developed antibodies that bind
specifically to PSCA, and extensively engineered and tested PSCA CAR T cell therapy in laboratory models of
prostate cancer. Recently, we have also found that another protein, carcinoembryonic antigen related cell
adhesion molecule 5 (CEACAM5), is expressed on the surface of most NEPCs.
In the proposed research, we will initiate a phase I clinical trial to evaluate our PSCA CAR T cells in patients with
metastatic CRPC, and interrogate patient specimens to elucidate mechanisms of treatment resistance with
particular attention given to the emergence of NEPC. We will also engineer and evaluate CARs aimed at safely
and specifically targeting CEACAM5 in laboratory models of NEPC. Lastly, we will determine whether a strategy
combining PSCA CAR T and CEACAM5 CAR T cells can safely address tumor heterogeneity in CRPC by
eradicating both prostate adenocarcinoma and NEPC.

## Key facts

- **NIH application ID:** 10478990
- **Project number:** 5P50CA092131-19
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** OWEN N. WITTE
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $336,009
- **Award type:** 5
- **Project period:** 2002-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478990

## Citation

> US National Institutes of Health, RePORTER application 10478990, Project 3: Developing CAR T Cell Therapies to Target Tumor Heterogeneity in Advanced Prostate Cancer (5P50CA092131-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10478990. Licensed CC0.

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