# Bispecific molecules linking T cell receptor and tumor antigen for cancer immunotherapy

> **NIH NIH U01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2023 · $79,874

## Abstract

PROJECT SUMMARY
T cells are responsible for the eradication infectious or cancerous cells in the body; however, cancer cells are
capable of evading T cell recognition and activation. Bispecific molecules are an emerging treatment option for
cancer immunotherapy that enhances the T cell’s ability to recognize cancerous cells and perform an immune
response. Their mechanism of action is to increase T cell sensitivity to cancer cells and efficacy by binding to
both T cells and the cancerous pMHC. Limitations in current designs include the inability to predict T cell
activation after binding and in efficacy for treating cancer. The objective of this proposal is to expand our
understanding of the factors that affect efficacy of bispecific molecules to enhance T cell performance. We
hypothesize that force dependent binding and docking orientation impact the overall efficacy of bispecific
molecules. The two specific aims are:
Aim 1. Identify the determining factor(s) of the anti-tumor efficacy of bispecific molecules
Aim 1A. Determine the 2D affinity and force dependent bond lifetime between several ImmTAC vs. pHLA and
vs CD3, thereby providing a unique dataset only our lab is capable to obtain.
Aim 1B. Examine the correlation, or the lack thereof, between the biophysical characteristics of the interactions
measured in 1A with the biochemical characteristics and biological functions of the ImmTAC molecules,
thereby shedding light on the determinant of their therapeutic efficacy
Aim 2. Assess how the pMHC docking orientation affects anti-tumor efficacy of the TCR
Aim 2A. Determine 2D affinity and force dependent bond lifetime for canonical and reversed orientation TCRs.
Aim 2B. Determine if the absence of CD8 is responsible for low efficacy when TCR is in reversed orientation.
Completing these aims will provide a new perspective on the considerations to be taken when designing
bispecific molecules for cancer immunotherapy.

## Key facts

- **NIH application ID:** 10747580
- **Project number:** 3U01CA250040-04S1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Rafi Ahmed
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $79,874
- **Award type:** 3
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747580

## Citation

> US National Institutes of Health, RePORTER application 10747580, Bispecific molecules linking T cell receptor and tumor antigen for cancer immunotherapy (3U01CA250040-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10747580. Licensed CC0.

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