Development of CAR-T Cells for T-ALL Targeting CCR9

Discover a groundbreaking webinar exploring the developments in cancer immunotherapy targeting CC chemokine receptor 9 (CCR9), a potential breakthrough for T-cell acute lymphoblastic leukemia (T-ALL). CCR9 is a potential cancer immunotherapy target, expressed in the majority of cases of T-ALL but only in a small proportion of normal immune and thymic cells. Thus, an immunotherapy targeted against CCR9 may be able to kill T-ALL cells while preserving critical normal T cells. GenScript has recently demonstrated that chimeric antigen receptor (CAR)-T cells targeting CCR9 were potent in in vitro and murine models of T-ALL and will shortly commence a Phase I clinical trial of anti-CCR9 CAR-T in relapsed or refractory T-ALL.

CCR9 is a complex and challenging target antigen. It is a G-protein coupled receptor with seven transmembrane domains. There is high homology between rodent and human sequences with most differences located intracellularly or at the amino terminus. Thus, developing specific antibodies to CCR9 is difficult, and a previous rat vaccination yielded only a single antibody clone.

In a new binder discovery campaign, multiple approaches were used to develop binders to CCR9, including DNA and RNA vaccination of both mice and rabbits. Despite initial challenges, several highly specific anti-CCR9 clones were obtained using RNA vaccination, with differing epitopes and biophysical characteristics. These clones are now being tested in antibody-drug conjugate and bispecific T-cell engager formats for potency in T-ALL and other conditions.

Further, using in silico design and experimental validation, optimized humanized versions of the initial anti-CCR9 antibody and single-chain fragment variable (scFv) which retained the binding characteristics and potency of the original clone were developed. Finally, using protein vaccination of rabbits, an anti-idiotype reagent to the original scFv, which will be used to track CAR-T in patients was developed.

Join this webinar to gain insights into advancements in T-ALL immunotherapy using CAR-T cells targeting the CCR9 receptor.