Human scFv based, ALPPL2-specific CAR expressing T cells induce potent antitumor activity in an IL15-dependent manner

Immune recognition of murine proteins expressed in adoptively transferred T cells and lack of homeostatic in the tumor microenvironment can limit expansion and persistence of CAR T cells. CARs generated only from human sequences reduce the risk of immune mediated rejection and Interleukin-15, which promotes T cell survival and fitness can improve the expansion and persistence of T cells.

In this study, we report a CAR T construct (ABBz) assembled from only human sequences including an scFv specific to ALPPL2 selected through an unbiased, high-throughput screen of human antibody-based, phage-displayed scFv library based on binding specificity, stringency, and low dissociation constant. We demonstrate specificity to the antigen, effective cytolytic function, and cytokine production induction in ABBz T cells.