On June 6, 2022 Eureka Therapeutics, Inc., a clinical-stage biotechnology company developing novel T cell therapies to treat solid tumors, reported the publication of a preclinical study in blood entitled "A TCR Mimic CAR T Cell Specific for NDC80 Is Broadly Reactive With Solid Tumors and Hematological Malignancies" (Press release, Eureka Therapeutics, JUN 6, 2022, View Source [SID1234615648]). The study was led by Dr. Cheng Liu, President & Chief Executive Officer of Eureka and Dr. Martin Klatt and Dr. David Scheinberg of Memorial Sloan Kettering Cancer Center (MSK).
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Chimeric antigen receptor (CAR) T cells represent a novel class of FDA-approved drugs with high efficacy against refractory B cell-derived malignancies. However, target identification and selection for CAR T cell therapy remains challenging as most cell surface proteins are not cancer-specific and therefore often not adaptable for CAR T cell therapy. In contrast, many intracellular proteins are highly tumor-specific and targetable after being presented on the cell surface by human leukocyte antigen (HLA) complexes in the form of peptide-MHC complexes. T cell receptor mimic (TCRm) antibodies can recognize peptide-MHC complexes similarly to TCRs, but with the versatility and applicability of an antibody.
In collaboration with MSK, Eureka scientists used its E-ALPHA platform to identify TCRm antibodies that target the NDC80-derived complex. NDC80 is an intracellular protein over-expressed in multiple tumor types such as ALL, AML, lymphoma, melanoma, mesothelioma, pancreatic and thyroid cancer. In the study, anti-NDC80 TCRm-redirected T cells demonstrated high specificity in recognizing and killing multiple cancer cell lines. Moreover, no toxicities to healthy leukocytes and hematopoietic stem cells were observed.
"TCR mimic antibodies can unlock the potential of T-cell therapies by targeting intracellular proteins that are presently not druggable by conventional antibodies or conventional CAR-T cells that target cell surface proteins," said Dr. Cheng Liu, Founder and CEO, Eureka Therapeutics. "We are excited by the study and look forward to seeing the expanded use of TCR mimic antibodies in other cancer types."