Re­sis­tant to CAR-T ther­a­pies? It's the can­cer, not your im­mune sys­tem — study

Safe­ty con­cerns and man­u­fac­tur­ing short­com­ings aside, ex­ist­ing CAR-T ther­a­pies — No­var­tis’ Kym­ri­ah and Gilead’s Yescar­ta — sim­ply don’t work in 10% to 20% of pa­tients with B cell ma­lig­nan­cies. What fac­tors un­der­pin this re­sis­tance to CAR-T ther­a­py? The main cul­prit could be the can­cer cells them­selves, ac­cord­ing to a team of re­searchers at Penn.

CAR-T ther­a­pies are en­gi­neered to work in this way: Cells are ex­tract­ed from the pa­tient and then ma­nip­u­lat­ed in a lab where chimeric anti­gen re­cep­tors are added to di­rect the pa­tient’s own T cells to snuff out spe­cif­ic can­cer cells once re-in­fused back in­to the pa­tient. But in a frac­tion of pa­tients, the armed im­mune at­tack does not oblit­er­ate the dis­ease. By tar­get­ing CD19, a mark­er present on al­most all B cells, CAR-T ther­a­pies have shown re­mark­able po­ten­cy and dura­bil­i­ty in a num­ber of blood can­cers, in­clud­ing acute lym­phoblas­tic leukemia (ALL).

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