Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions
CAR T signaling strength analyzed in preclinical study
Salter AI et al., Sci Signal. 2018 Aug 21;11. pii:eaat6753.
Key clinical point: Increased speed or strength of intracellular signaling may, counterintuitively, limit efficacy of CAR T-cell therapy.
Major finding: T cells with a CD28 CAR had very strong initial antitumor function that quickly waned in a mouse model of lymphoma, while the 4-1BB CAR signal led to T cells that better retained their function in vivo and had a longer median survival in the model.
Study details: Analysis of CARs encoding CD28 or 4-1BB costimulatory domains in primary human T cells using mass spectrometry, plus analysis of efficacy in a mouse model of lymphoma.
Disclosures: Study authors reported disclosures related to Juno therapeutics and a patent application related to use of mutant CD28 CARs for cellular therapy.
Salter AI et al., Sci Signal. 2018 Aug 21;11. pii:eaat6753.
