Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial successes against B-cell malignancies, what has led to a growing scientific and clinical interest on extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immuno-suppressive tumour microenvironment, that is able to inactivate CAR-T cell clones.
MOLAB researchers have put forward a mathematical model describing the competition of CAR-T and tumour cells, accounting for their immunosuppressive capabilities. Using the mathematical model, they proposed and studied computationaly, the manufacture and injection of CAR-T cells targeting two antigens: CD19 and a tumour-associated antigen. The strategy led to the massive generation of an army of CAR-T cells targetting the solid tumour in-silico, and potentially overcoming its inmune suppression capabilities. That strategy could further benefit from the combination with PD-1 inhibitors and of low tumour loads.
León-Triana, O.; Pérez-Martínez, A.; Ramírez-Orellana, M.; Pérez-García, V.M. Dual-Target Car-Ts With on- and off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept. , 2020120166 (doi: 10.20944/preprints202012.0166.v1).