# Catch and Release Immunotoxins: CAR-Bombs for Cancer

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $364,227

## Abstract

Abstract
The American Cancer Society estimates that in 2016 there will be 1.7 million new cancer cases diagnosed and
600,000 cancer deaths in the United States. Although advances have been made in the treatment of cancer
with surgery, radiation, chemotherapy, and with biologics, there is a critical need to develop novel treatment
approaches with promise for improved selectivity, potency, and efficacy. This project introduces a new and
previously untested platform strategy to enhance the efficiency of delivery of macromolecules to the cytoplasm
of targeted cells. The central component of the strategy is the use of “catch-and-release” monoclonal
antibodies (CAR), with pH-dependent receptor binding. The CAR antibodies are conjugated to highly potent
macromolecular toxins (CAR-toxin) and to endosome escape peptides (CAR-EEP). Combined administration
of CAR-toxin and CAR-EEP conjugates allows efficient, targeted delivery and release of the toxin in the
cytoplasm, enabling highly selective and potent anti-cancer efficacy. To pursue this project, we have
developed a novel catch-and-release anti-carcinoembryonic antigen (CEA) antibody (10H6), with high affinity
CEA binding at physiological pH, and with dramatically reduced binding at acidic pH. Preliminary data have
been generated to assess the binding, cytotoxicity, and pharmacokinetics of 10H6, which in sum, strongly
support the feasibility of the work. An interdisciplinary team has been assembled to evaluate this approach,
with three experimental aims that will: (1) examine and optimize the utility of catch and release conjugates for
cytoplasmic delivery of macromolecules to cancer cells in vitro, (2) test hypotheses regarding the tumor
selectivity of in vivo disposition of the antibody conjugates, and (3) evaluate the safety and efficacy of the
catch-and-release mAb conjugates in the treatment of mice bearing human xenograft tumors. The project, if
successful, will establish a new targeting concept, with potential utility in enhancing the efficiency of
cytoplasmic delivery of virtually any macromolecule to any type of cancer.

## Key facts

- **NIH application ID:** 10062878
- **Project number:** 5R01CA204192-05
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Joseph P Balthasar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $364,227
- **Award type:** 5
- **Project period:** 2016-12-07 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062878

## Citation

> US National Institutes of Health, RePORTER application 10062878, Catch and Release Immunotoxins: CAR-Bombs for Cancer (5R01CA204192-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10062878. Licensed CC0.

---

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