CD28 signaling complexes are correlated with patient outcomes in anti-CD19 41BB-costimulation CAR T cell therapy.

ABSTRACT:

Background

Chimeric antigen receptor (CAR) T cells targeting CD19 achieve remarkable remissions in refractory B cell malignancies, yet deleterious side effects such as cytokine release syndrome (CRS) limit their broader application. Current preclinical assays on manufactured cell products do not predict human clinical function. We hypothesized that variability in the CAR proximal protein interaction networks that mediate CAR signal transduction may correlate with patient-to-patient differences in toxicity.

Methods

Using banked, preinfusion 41BB-CD3ζ CAR T cell products with known clinical outcomes, we applied quantitative multiplex co-immunoprecipitation (QMI) to profile ∼200 binary interactions among 21 key signaling proteins following CD19 stimulation. Bioinformatic analys

SUBMITTER: Draper IH 

PROVIDER: S-EPMC12636892 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature