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Immunotherapy using CAR T-cells

Publication at Faculty of Medicine in Pilsen |
2015

Abstract

A central role of T-cells in the control of cancer has been supported by both animal models and clinical observations. Adoptive cell therapy has recently achieved impressive efficacy, supporting the finding that the immune system can fight cancer.

The broaden application of cell immunotherapy has been previously constrained by the technical abilities to isolate and expand antigen-specific T-cells potent to selectively kill tumor cells. One of the promising current strategies is based on ex vivo engineered patients T-cells, which are redirected by a chimeric antigen receptor (CAR).

Chimeric antigen receptors usually combine the antigen binding site of a monoclonal antibody with the effector function of a T -cell. The genetic manipulation gives T-cells desired specificity but also enables to tailor their activation and proliferation potential.

Such modified CAR T-cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. Various CAR designs, manufacturing processes, and study populations have been tested.

CAR T-cells represent a powerful therapeutic approach, especially in hematologic malignancies. Administration of CD19-specific CAR-modified T cells, that target B-cell, in non-Hodgkin lymphomas and chronic lymphocytic or acute lymphoblastic leukemia, has been remarkably effective in recent clinical trials.

The future research has to identify the critical parameters of CAR T-cells design and engineering that are necessary for effective utilization of adoptive T-cell transfer in cancer therapy. Finally, the personalized cell therapy may expand as a promising treatment approach to different hematologic malignancies and solid tumors.