Jul 6, 2021 · Herein, we provide an overview of T cell costimulation by CD28 and 4-1BB and, using the available preclinical and clinical data, compare the efficacy and toxicity profiles associated with CARs...

Aug 31, 2024 · Here, we apply biophysical methods to characterize the structure and dynamic properties of the CD28 CAR hinge (CD28H) used in an FDA-approved CD19 CAR for the treatment of B-lineage...

Mar 3, 2025 · These findings provide new insights into how CD28 costimulation boosts CAR-NK cell efficacy, supporting its use into NK cell-specific CARs for cancer immunotherapy, and highlight MAP3K8 as a potential target for optimizing BBz CAR-NK cell therapy.

May 20, 2020 · CD28-based CARs seem to elicit stronger T cell activation as compared with 4-1BB–expressing CARs, tending toward an effector-like phenotype, with high interleukin-2 (IL-2) secretion and cytolytic capacity; they are sensitive to low antigen levels and highly proliferative and glycolytic (2, 10, 11).

Second generation (2G) chimeric antigen receptors (CARs) contain a CD28 or 41BB co-stimulatory endodomain and elicit remarkable efficacy in hematological malignancies. Third generation (3G) CARs extend this linear blueprint by fusing both co-stimulatory units in series.

Mar 23, 2021 · CARs containing a CD28-TMD, but not a CD8-TMD, formed heterodimers with the endogenous CD28 in human T cells, as shown by co-immunoprecipitation and CAR-dependent proliferation of anti-CD28 stimulation.

Jun 27, 2024 · CD28 and 4-1BB costimulatory endodomains included in chimeric antigen receptor (CAR) molecules play a critical role in promoting sustained antitumor activity of CAR-T cells.

Jun 18, 2020 · In CD28ζ CAR, CD28 and CD3ζ domain are fused together to implement signal transduction. Therefore, it is assumed that the synergetic effect of CD3 and CD28 signaling also plays a crucial role in regulating downstream signaling and affecting T cell function.

Feb 17, 2025 · The CD28/CD3ζ costimulatory molecule in traditional CAR constructs reprograms CAR-T-cell metabolism toward glycolysis; impairs T-cell activation, proliferation, and persistence after 14 days of in vitro culture; and promotes effector memory T-cell differentiation . However, there is also evidence that Fcγ-CR and CD32/CD28/CD3ζ T cells ...

Mar 3, 2025 · Our study confirms CD28’s advantages and, through RNA-Seq and functional experiments, reveals how CD28 costimulation rewires activation networks in CAR-NK cells. We also identified MAP3K8, a key regulator of the MEK1/2-ERK1/2 pathway [3, 4], as crucial for enhancing CAR-NK cell function.