# Secretable theranostic payloads to augment the efficacy of adoptive CAR-T cell therapies

> **NIH NIH R21** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $455,112

## Abstract

PROJECT SUMMARY
The ability to genetically engineer primary T-cells creates new and highly promising prospects for tumor
immunity and cancer treatment. Specifically, the transduction of T-cells with genes encoding chimeric antigen
receptors (CARs) and therapeutic payloads enables T-cells to recognize antigens that are either poorly
immunogenic or ignored by the immune system, and to successfully eradicate tumors. One of the major
impediments of genetically engineered CAR-T-cell technology is the heterogeneity of targeted antigens and
antigen escape from tumors. In this application we propose to develop and test a novel theranostic approach to
augment apoptosis in tumors with heterogeneous antigen levels using antibody-based secretable payloads
(ASPs) delivered by antigen-specific T cells under image guidance. We hypothesize that secretion of tumor-
directed ASPs by antigen-specific CAR-T cells will induce/augment apoptosis in tumors with heterogeneous
tumor antigen levels. This proposal brings together translatable antibody-based therapeutics and reporter gene
imaging components in genetically engineered T-cells, allowing for non-invasive monitoring of T-cell trafficking,
tumor targeting, and secretion of ASPs. We expect that genetically engineered T-cells will secrete ASPs into
the tumor microenvironment, thus inducing apoptosis in a larger number of tumor targets including antigen-
negative tumors. Our proposal complements the ongoing genetically engineered CAR-T cell clinical studies at
MSK by exploring new strategies designed to enhance tumor targeting and T-cell effector function and to
improve treatment response in tumors with heterogeneous targeted antigen levels.

## Key facts

- **NIH application ID:** 10072492
- **Project number:** 1R21CA250478-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Vladimir Ponomarev
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $455,112
- **Award type:** 1
- **Project period:** 2020-08-03 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072492

## Citation

> US National Institutes of Health, RePORTER application 10072492, Secretable theranostic payloads to augment the efficacy of adoptive CAR-T cell therapies (1R21CA250478-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072492. Licensed CC0.

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