A NOVEL TRuC™ PLATFORM FOR SOLID AND HEMATOLOGIC CANCERS WITHOUT THE NEED FOR HLA MATCHING
T Cell Therapy: Harness the Power of Living Immune Cells to Fight Cancer
Complete TCR Complex on T Cell is Needed to Address Solid Tumors
Existing CAR and Engineered TCR Therapies Have Key Limitations
The engineered TCR approach which utilizes the complete TCR has shown clinical activity in solid tumors, but there are major limitations to this approach associated with HLA which is required for TCR to bind to tumor antigen10,11. Specifically, HLA is often downregulated on cancer cells, blinding T cells from recognizing them, and current TCR-T cell approaches are only applicable to individuals expressing specific HLA subtypes (most frequently those expressed by patients of European descent such as HLA-A2) preventing the universal applicability of such technology.
The TRuC™ Platform Overcomes CAR-T and TCR Limitations
TRuC™-T cells have demonstrated superior anti-tumor activity in vivo compared to CAR-T cells while releasing a lower level of cytokines. In vivo studies also showed long persistence of TRuC™-T cells in animal models for over 100 days. These data are particularly encouraging for solid tumors where CAR-T cells have not shown significant clinical activity likely due to very short persistence and in hematologic tumors where a high incidence of severe cytokine release syndrome remains a major concern.
The TRuC™ Platform Has Great Versatility
Each vehicle can also be engineered to carry built-in modulators (accessories) that further potentiate T cell activity in the presence of specific negative elements of the hostile tumor microenvironment.
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10 Robbins, P. F. et al. (2015). A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clinical Cancer Research, 21(5):1019-27
11 Lu, Y. C. et al. (2017). Treatment of Patients With Metastatic Cancer Using a Major Histocompatibility Complex Class II–Restricted T-Cell Receptor Targeting the Cancer Germline Antigen MAGE-A3. Journal of Clinical Oncology, 35, no. 29 (October 2017) 3322-3329.