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Augmenting CAR T Cell Functions with LIGHT.

Winson CaiKento TanakaXiaoli MiVinagolu K RajasekharJonathan F KhanSarah YooElisa De StanchinaJahan A RahmanSerena MathewParwiz AbrahimiSydney SounessTerence J PurdonJames R McDowellJeremy MeyerbergTakeshi FujinoJohn H HealeyOmar Abdel-WahabDavid A ScheinbergRenier J BrentjensAnthony F Daniyan
Published in: Cancer immunology research (2024)
Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success in the treatment of B-cell malignancies. However, its clinical efficacy in solid tumors is limited, primarily by target antigen heterogeneity. To overcome antigen heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand of both LTβR on cancer cells and HVEM on immune cells. LIGHT-expressing CAR T cells displayed both antigen-directed cytotoxicity mediated by the CAR and antigen-independent killing mediated through the interaction of LIGHT with LTβR on cancer cells. Moreover, CAR T cells expressing LIGHT had immunostimulatory properties that improved the cells' proliferation and cytolytic profile. These data indicate that LIGHT-expressing CAR T cells may provide a way to eliminate antigen-negative tumor cells to prevent antigen-negative disease relapse.
Keyphrases
  • cell therapy
  • stem cells
  • signaling pathway
  • oxidative stress
  • cell proliferation
  • machine learning
  • deep learning
  • big data
  • wild type