Triple knockdown of CD11a, CD49d, and PSGL1 in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice

Science TLDR by Raymond Ruff

E24
14:16
Episode notes

DOI: 10.1126/scitranslmed.adl6432

Key Points:

  1. The Research Problem:
  • CAR-T cell therapy has been successful for blood cancers but faces challenges with solid tumors
  • Major challenge: "On-target, off-tumor toxicity" where CAR-T cells attack healthy tissues
  • Previous patient death case: HER2-targeted CAR-T cells attacked lung tissue due to HER2 expression on lung cells
  1. Study Focus:
  • Target: EpCAM (epithelial cell adhesion molecule) found on many solid tumors
  • Challenge: EpCAM is also present in normal tissues, raising toxicity concerns
  • Goal: Fine-tune CAR-T cells to attack tumor cells while sparing healthy  ... 
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