Matches in SemOpenAlex for { <https://semopenalex.org/work/W4381890138> ?p ?o ?g. }
- W4381890138 abstract "Abstract Adoptively transferred T cells and agents designed to block the CD47/SIRPα axis are promising antitumor therapeutics, which activate distinct arms of the immune system. We administered anti-CD47 (αCD47) with adoptively transferred T cells with the goal of enhancing antitumor efficacy but observed rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors, which blunted therapeutic benefit. αCD47 mediated CAR T clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered a CD47 variant (47 E ) that engaged SIRPα and provided a “don’t-eat-me” signal that was not blocked by αCD47 antibodies. TCR or CAR T cells expressing 47 E were resistant to clearance by macrophages following αCD47, and mediated significant, sustained macrophage recruitment into the TME. Although many of the recruited macrophages manifested an M2-like profile, the combined therapy resulted in synergistic enhancement in antitumor efficacy. This work identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T cell directed therapeutics with those designed to activate macrophages. It further delivers a therapeutic approach capable of simultaneously harnessing the antitumor effects of T cells and macrophages that manifests markedly enhanced potency against solid tumors." @default.
- W4381890138 created "2023-06-25" @default.
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- W4381890138 date "2023-06-22" @default.
- W4381890138 modified "2023-10-16" @default.
- W4381890138 title "Engineered CD47 protects T cells for enhanced antitumor immunity" @default.
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