CD19 CAR T cells with mutant CD28 co-stimulatory domain

CD19 CAR T cells with a mutant CD28 co-stimulatory domain (often referred to as mut06) are an experimental form of adoptive cellular immunotherapy designed to treat B-cell malignancies. This construct consists of T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the CD19 antigen, coupled with a modified CD28 intracellular signaling domain. In this mutant domain, specific signaling motifs associated with T-cell exhaustion and limited persistence—namely the YMNM (Grb2-binding) and PRRP (PLCγ-binding) motifs—are eliminated or modified. By selectively retaining or adding motifs (such as TRAF-binding motifs from 4-1BB or CD40), these CAR T cells aim to combine the rapid, potent anti-tumor activation characteristic of CD28 with the superior metabolic fitness and long-term survival typically associated with 4-1BB co-stimulation. Research, including work presented by Factor Bioscience, has also explored the site-specific integration of these CARs into the TRAC locus to further optimize physiological expression and reduce tonic signaling.

Other names

mut06 CAR T cellsmut-06 CAR T cellsmut 06 CAR T cellsCD19-CD28mut CAR-TCD-19-CD28mut CAR-TCD 19-CD28mut CAR-TCD19 CAR T cells with mut06 CD28 domainCD-19 CAR T cells with mut06 CD28 domainCD 19 CAR T cells with mut06 CD28 domain