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Highly active CAR T cells that bind to a juxtamembrane region of mesothelin and are not blocked by shed mesothelin.

Xiufen LiuMasanori OndaNathan WatsonRaffit HassanMitchell HoTapan K BeraJunxia WeiAnirban ChakrabortyRichard BeersQi ZhouAsif ShajahanParastoo AzadiJingyu ZhanDi XiaIra H Pastan
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
SignificanceMesothelin (MSLN) is a cell-surface protein that is a popular target for antibody-based therapies. We have identified shed MSLN as a major obstacle to successful antibody therapies and prepared a monoclonal antibody that inhibits shedding and makes very active CAR T cells whose activity is not blocked by shed MSLN and merits further preclinical development.
Keyphrases
  • monoclonal antibody
  • cell surface
  • induced apoptosis
  • cell cycle arrest
  • endoplasmic reticulum stress
  • stem cells
  • cell death
  • cell therapy
  • oxidative stress
  • bone marrow
  • small molecule