CAR‑T treatment in oncology and hematooncology

Supplementum 01/2019 Imunoterapie

Doc. MUDr. Daniel Lysák, Ph.D.

Hematologicko-onkologické oddělení FN Plzeň

SUMMARY

Progress in our understanding of tumor immunology together with advances in cell engineering and cultivation have made possible the production of modified T-lymphocytes expressing the chimeric antigen receptor (CAR). This new technology has emerged as an effective modality in many tumors even for diseases refractory to conventional chemotherapy. The lymphocytes are processed ex vivo and after re-infusion are able to recognize and kill the tumor cells. The most notable success has been achieved with the CAR-T cells specific to CD19 antigen, which possess significant antitumor activity in patients with relapsing and refractory B-lymphoid malignancies (ALL, NHL). CAR-T cell therapy may lead to substantial adverse reactions including the cytokine release syndrome or neurotoxicity effects. The list of targetable antigen and indications is continuously being expanded. The efficacy of treatment is also verified in solid tumors, however the results are less encouraging. The modifications to the CAR structure and the final product are under investigation. The research is also focused on understanding the mechanisms of relapses, reducing toxicities and development of the principles of synthetic biology. CAR therapy is still in an early stage of development and they are many possibilities for improvements in its various aspects for the next years. The article summarizes the current status, challenges and potential future trends of CAR therapy.

KEY WORDS

CAR, chimeric antigen receptor, T-lymphocyte, CD19, immunotherapy, biological treatment