The journal Nature Medicine recently published a study in which researchers developed a novel receptor to enhance recognition of tumors by engineered T cells, addressing an underlying cause for relapsed tumors in patients after chimeric antigen receptor therapy. The study demonstrates high antigen sensitivity of HLA-independent T-cell receptors, created by editing the TCR Alpha Constant chain locus in human peripheralbio blood Tcells.
Low antigen expression
One major limitation of CARs is antigen escape, when a tumor no longer expresses the antigen detectable by the CARs or expresses them at a very low level; CARs with heightened sensitivity to low-expression level antigens boosts the efficacy of otherwise promising T-cell therapies.
In the study, conducted by researchers at New York's Memorial Sloan Kettering Cancer Center, researchers produced HIT T-cells and analyzed them in animal models
HIT T-cells were engineered from human peripheral blood T-cells by inserting variable region genes in the TRAC locus, endowing the cell with a single specificity for a target antigen such as CD19. Notably, this sensitivity was shown to be higher than traditional CARs for low levels of antigen expression resulting in superior cytotoxicity and cytokine secretion.
HIT Tcells outperformed traditional CAR T-cells in vivo in mouse models of B cell leukemia and acute myeloid leukemia, without costimulation. Coexpression of HIT with CD80 and 4-1BBL further augmented therapeutic activity and mouse survival.
HIT T-cells are a promising therapy for targeting cancer cell surface antigens with low abundance due to their sensitivity and persistence.
The team responsible for this important work includes MSKCC researcher and Mnemo Therapeutics scientific cofounder Michel Sadelain, M.D., Ph.D., MSKCC researcher and Mnemo scientific advisor Isabelle Rivière, Ph.D., as well as Justin Eyquem, Ph.D., University of California San Franciso and Mnemo scientific cofounder.
Mnemo's EnfiniT Platform
These findings support Mnemo's EnfiniT platform as the next-generation toolkit for CAR-T immunotherapies, which are founded on decades of breakthrough research from Institut Curie and MSKCC, and supported with best-in-class T-cell manufacturing. The EnfiniT platform brings together a suite of technologies to address the key challenges associated with CAR T therapies by both identifying a new class of antigens with greater tumor specificity and applying a range of technologies to significantly improve T-cell memory, persistence and sensitivity. The goal is to dramatically improve the body's ability to fight and overcome disease.
About Mnemo Therapeutics
Mnemo Therapeutics is a biotechnology company focused on the development of powerful new cell therapies. With its EnfiniT platform, Mnemo applies a novel, integrated approach to T-cell therapy to transform the body's immune response to overcome disease. Mnemo is headquartered in Paris with an office in New York City, and it maintains state of the art laboratories in Paris, New York, and Princeton, New Jersey. The company leverages an international talent pool and global resources in its quest to create accessible cures for all patients in need.