T Cell Receptor Mimic Antibodies for Cancer Therapy

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2016 Mar 5

PMID 26942058

Citations 26

Authors

Leonid Dubrovsky

Tao Dao

Ron S Gejman

Elliott J Brea

Aaron Y Chang

Claire Y Oh

Emily Casey

Dmitry Pankov

David A Scheinberg

Affiliations

Soon will be listed here.

Abstract

The major hurdle to the creation of cancer-specific monoclonal antibodies (mAb) exhibiting limited cross-reactivity with healthy human cells is the paucity of known tumor-specific or mutated protein epitopes expressed on the cancer cell surface. Mutated and overexpressed oncoproteins are typically cytoplasmic or nuclear. Cells can present peptides from these distinguishing proteins on their cell surface in the context of human leukocyte antigen (HLA). T cell receptor mimic (TCRm) mAb can be discovered that react specifically to these complexes, allowing for selective targeting of cancer cells. The state-of-the-art for TCRm and the challenges and opportunities are discussed. Several such TCRm are moving toward clinical trials now.

Citing Articles

design and structure of a peptide-centric TCR mimic binding module.

Householder K, Xiang X, Jude K, Deng A, Obenaus M, Wilson S bioRxiv. 2025; .

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Molecular basis for antibody recognition of multiple drug-peptide/MHC complexes.

Maso L, Rajak E, Bang I, Koide A, Hattori T, Neel B Proc Natl Acad Sci U S A. 2024; 121(22):e2319029121.

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Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.

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Conformation-selective rather than avidity-based binding to tumor associated antigen derived peptide-MHC enables targeting of WT1-pMHC low expressing cancer cells by anti-WT1-pMHC/CD3 T cell engagers.

Walseng E, Wang B, Yang C, Patel P, Zhao C, Zhang H Front Immunol. 2023; 14:1275304.

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Effects of HLA single chain trimer design on peptide presentation and stability.

Finton K, Rupert P, Friend D, Dinca A, Lovelace E, Buerger M Front Immunol. 2023; 14:1170462.

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