# T-cell engaging bispecific antibodies designed for proteolytic activation in the tumor microenvironment

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2022 · $211,895

## Abstract

PROJECT SUMMARY
In response to NCI’s FOA PAR-20-292 for early and conceptual stages of translational cancer research, our
NIH R21 grant application seeks the generation and validation of a new format of conditionally active T-cell
engaging bispecific antibodies (T-biAbs) designed for proteolytic activation in the tumor microenvironment of
solid malignancies. As such, the proposed T-biAb format permits the targeting of tumor-associated antigens
(TAAs) that prohibit interrogation by conventional T-biAbs due to their basal expression levels on healthy cells
of vital organs. While such conditionally active T-biAbs have broad therapeutic utility, we will focus our
proposed studies on rigorously validating the new format in in vitro, in vivo, and ex vivo models of ovarian
cancer. This includes experiments with both ovarian cancer cell lines (in vitro and in vivo) and primary tumor
cells from ovarian cancer patients (ex vivo). There is an urgent public health need for conceptually new
treatments for ovarian cancer. Less than half of the ~235,000 U.S. women currently living with ovarian cancer
will survive 5 years. In 2020, ~22,000 U.S. women will be newly diagnosed and ~14,000 will die of ovarian
cancer. We will test the hypothesis that conditionally active T-biAbs targeting the TAAs EGFR, HER2, and
FOLR1, all of which are overexpressed in ovarian cancer, can mediate potent and safe eradication of tumor
cells. With the overall objective of incentivizing advanced preclinical investigations, we will deliver both
innovative tools and techniques for probing TAA targeting with conditionally active T-biAbs designed for
proteolytic activation in the tumor microenvironment of solid malignancies in general and ovarian cancer in
particular.

## Key facts

- **NIH application ID:** 10454413
- **Project number:** 5R21CA263240-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** CHRISTOPH RADER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $211,895
- **Award type:** 5
- **Project period:** 2021-07-20 → 2023-03-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454413

## Citation

> US National Institutes of Health, RePORTER application 10454413, T-cell engaging bispecific antibodies designed for proteolytic activation in the tumor microenvironment (5R21CA263240-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454413. Licensed CC0.

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