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S9-4
Chimeric antigen receptor T cells review: from bench to bedside
林建廷Chien-ting Lin
Tai-Cheng stem cell therapy center, National Taiwan university
Division of hematology, Department of internal medicine, National Taiwan university Hospital
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CART19 therapy, from Novartis and Kite, was approved by FDA in 2017 to treat relapsed and refractory B-ALL and B-cell lymphoma, respectively, and CART is now moving to the market. We will have a quick review of current advance in the field of chimeric antigen receptor T cells, including its design, manufacture, and clinical trial results. Regarding its design, co-stimulating domain such as 41BB or CD28 is almost inevitable, however, there are several variations. How to manufacture CART19 to meet the GMP/ GMP-compliant requirement is also a critical and probably the most difficult point. Several phase 1 or 2 trials for patients with B-ALL or B-NHL have been reported and we will have a brief summary and highlight what we have learned from these trials.
We will also talk about the toxicities, such as cytokine releasing syndrome (CRS) and neurotoxicity. Tocilizumab (anti-IL6) is an antidot for CRS and it is quite important to reduce the side effects of CART19. Another small molecule, anakinra (anti-IL1Ra), has drawn our attention because the preliminary data show it may prevent neurotoxicity.
Finally, immune escape is still inevitable at least for some patients post-CART therapy. We will discuss its mechanism and how to reduce the possibility of immune escape. If possible, we will also talked about other CARTs other than CART19, for example anti-BCMA CART, anti-IL13Ra CART, and 7*19 CART for solid cancers. |
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