Marianna Csaplár, János Szöllősi, Stephen Gottschalk, György Vereb and Árpád Szöőr have investigated the role of differentiation on the anti-tumor activity of CAR T cells targeting the solid tumor antigen HER2 in preclinical models. Adoptively transferred T cells expressing recombinant chimeric antigen receptors (CAR T cells) have been approved for the therapy of hematological malignancies of the B cell lineage. However, CAR T cell therapy for patients with solid tumors so far has shown limited benefits. Correlative clinical studies of patients with hematological malignancies have suggested that less differentiated CAR T cells have improved anti-leukemic activity. They utilized different activation/expansion protocols, and explored whether different co-stimulatory domains in the CAR construct influence the short- and long-term efficacy of HER2-CAR T cells. We demonstrate that the CAR T cell product with the highest proportion of effector cells and maintaining a good balance of CD4+/CD8+ cells is the most effective against solid tumors both in vitro and in vivo.
Csaplár, M.; Szöllősi, J.; Gottschalk, S.; Vereb, G.; Szöőr, Á. Cytolytic Activity of CAR T Cells and Maintenance of Their CD4+ Subset Is Critical for Optimal Antitumor Activity in Preclinical Solid Tumor Models. Cancers 2021, 13, 4301.
https://www.mdpi.com/2072-6694/13/17/4301