What CAR Will Win the CD19 Race?

Adoptive transfer of T cells engineered with synthetic receptors is emerging as a new pillar in the treatment of cancer. The adoptive cell therapy furthest along in clinical development is the engineering of T cells to express chimeric antigen receptors (CAR) against the CD19 antigen. Several platforms have shown remarkable activity in patients with relapsed or refractory B-cell malignancies. In 2017, the FDA approved the first CAR T cell products tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Gilead), and others are expected to follow shortly. Despite their activity, CAR T cell approaches have limitations that will need to be addressed, including excessive toxicity, relapses mediated via antigen escape, difficulties overcoming the suppressive tumor microenvironment, high manufacturing costs and retail prices, and patient access, among others. The CAR T cell product that better addresses those challenges will obtain a critical competitive advantage.