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A platform for parallel TCR cloning and testing enables anti-neoantigen tumor immunotherapy
Alexander M Rowe1, Smriti Chaurasia1, Wenzhong Wei1,2
1Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
JCI Insight
|April 28, 2026
Summary
Researchers developed TCXpress to identify T cell receptors (TCRs) targeting cancer neoantigens. This platform enabled the discovery of TCRs that successfully treated mice with MC38 tumors, validating a potential new cancer therapy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- CD8 T cells recognize tumor neoantigens, but most patients do not respond to current immunotherapies.
- Understanding anti-tumor T cell responses is crucial for developing improved cancer treatments.
Purpose of the Study:
- To develop a high-throughput platform (TCXpress) for cloning and studying T cell receptors (TCRs) from tumor-infiltrating CD8 cells.
- To identify specific TCRs targeting neoantigens in mouse MC38 tumors and evaluate their therapeutic potential.
Main Methods:
- Applied TCXpress to clone TCRs from CD8 cells infiltrating MC38 tumors.
- Expressed cloned TCRs in reporter cells and tested specificity against neoantigen-presenting cells.
- Administered T cells engineered with anti-Rpl18 TCRs to MC38-bearing mice.
Main Results:
- Identified TCRs reactive against neoantigens from Rpl18, Adpgk, Psmd2, and Zc3h7b mutations.
- Isolated self-reactive TCRs that recognized normal B6 and MC38 cells.
- Successfully treated MC38-bearing mice using T cells transduced with anti-Rpl18 TCRs.
Conclusions:
- TCXpress provides a powerful system for studying T cell responses against tumor neoantigens.
- TCR-engineered T cells targeting specific neoantigens represent a viable therapeutic strategy for cancer treatment.
