Cytolytic Activity of CAR T Cells and Maintenance of Their CD4+ Subset Is Critical for Optimal Antitumor Activity in Preclinical Solid Tumor Models

2021, September 15 - 14:45
Cytolytic Activity of CAR T Cells and Maintenance of Their CD4+ Subset Is Critical for Optimal Antitumor Activity in Preclinical Solid Tumor Models

 

 

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

 


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