# Adapting 5MCAR technology for the treatment of peripheral T cell lymphoma

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2023 · $217,900

## Abstract

PROJECT SUMMARY
CD4+ T cells respond to peptide antigens presented by MHCII molecules (pMHCII) using a 5-module molecular
machines composed of a receptor module [the T cell receptor (TCR)], three signaling modules (CD3, CD3,
CD3), and a coreceptor module (CD4). Drawing upon this blueprint, we designed a biomimetic 5-module
chimeric antigen receptor (5MCAR) system composed of a chimeric receptor module, built with pMHCII and
TCR components (CRMpMHCII), that assembles with the CD3 signaling modules and works with a surrogate
coreceptor (ScoR) to generate signals in response to specific TCRs. As we recently reported (Kobayashi, et
al., PNAS 2020), 5MCAR-CTLs can specifically target and kill pathogenic CD4+ T cells that express TCRs that
bind the CRMpMHCII. Given that peripheral T cell lymphomas (PTCLs) represent a unique type of pathogenic T
cell for which treatment options are limited, and patient prognosis is poor, we are motivated to ask if our 5MCAR
technology can be developed into a patient-specific PTCL therapy. As PTCLs are often derived from
transformed CD4+ T cells and express a clonotypic TCR that represents a tumor-specific antigen, we
consider them to be ideal targets for 5MCAR-CTLs. Accordingly, the goal of the current study is to establish a
workflow whereby our 5MCAR technology is used to screen libraries of CRMpMHCII for mimotope CRMpMHCII that
signal in response to the clonotypic TCR of a PTCL, and then use the identified mimotope CRMpMHCII to
generate 5MCAR-CTLs for targeting the PTCL via its clonotypic TCR. When completed, the established
workflow will provide a blueprint for adapting our 5MCAR technology into a personalized therapy to treat
patients with PTCLs.

## Key facts

- **NIH application ID:** 10543167
- **Project number:** 5R21CA267071-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Michael S Kuhns
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $217,900
- **Award type:** 5
- **Project period:** 2022-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543167

## Citation

> US National Institutes of Health, RePORTER application 10543167, Adapting 5MCAR technology for the treatment of peripheral T cell lymphoma (5R21CA267071-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10543167. Licensed CC0.

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