Feb 21, 2023 · CD28 domain and the kinase FYN mediate this LCK-independent signaling. LCK-disrupted CAR-T shows increased in vivo anti-tumor efficacy—attributed to the improved memory/persistence and reduced exhaustion—and the potential for allogeneic use.

Dec 1, 2003 · In this review, we discuss recent genetic, biochemical and biophysical data that indicate a modified view of the molecular mechanism by which ligation of CD28 amplifies TCR-mediated T-cell...

Feb 21, 2023 · This LCK-independent signaling requires the related SFK FYN and a CD28 intracellular domain within the CAR. LCK-deficient CAR-T cells are strongly signaled through CAR and have better in vivo efficacy with reduced exhaustion phenotype and enhanced induction of memory and proliferation.

In this mini-review, we provide an up-to-date overview of our understanding of the signaling mechanisms that underlie CD28 function and its potential application to the modulation of reactivity to autoimmunity. Key words: CD28, co-stimulation, T cells, PI3K, Grb2, NFκB.

Dec 1, 2001 · CD28 crosslinking reduces the number of TCRs that need to be engaged, as well as the time required for T cells to interact with antigen, and enhances the magnitude of the T-cell response....

Jun 1, 1996 · Unlike growth factor receptors, CD28 lacks an intrinsic tyrosine kinase domain. What, then, is the kinase that initiates cosignaling by phosphorylating CD28? p56 lck and p59 fyn have been identified in expression studies as two kinases that phosphorylate CD28 and recruit PI 3-kinase and GRB-2 to the receptor (Raab et al. 1995).

CD28 domain and the kinase FYN mediate this LCK-independent signaling. LCK-disrupted CAR-T shows increased in vivo anti-tumor efficacy—attributed to the improved memory/persistence and reduced exhaustion—and the potential for allogeneic use.

Dec 5, 2005 · CD28 co-localizes with Fyn molecules that contain the N terminus and a functional SH2 domain. These results suggest that Fyn association with the TCR-CD3 complex, CD45 and CD28 is mediated by different molecular mechanisms.

Oct 1, 2007 · Inclusion of anti-CD28 Ab during stimulation enhanced production of IL-2 by ∼50% for both Fyn −/− and WT cells (Fig. 3 C); however, Fyn −/− cells still consistently produced more IL-2 than controls.

Feb 2, 2023 · In summary, these data suggest that tilting CD28-CAR-T activation toward FYN via disruption of LCK expression, results in a more proliferative, memory-retaining, and less exhausted phenotype, explaining the enhanced therapeutic performance of disLCK-CAR-T …