With the goal of improving outcomes and treatment options for patients with relapsed or refractory B-cell lymphoma, Aranda-Orgilles et al. generated an allogeneic TRAC-/CD52- dual CD20x22 CAR from healthy T cell donors. Preclinically, allogeneic CD20x22 CAR T cells exhibited strong, sustained, and dose-dependent cytolytic activity against tumor cells expressing one or both antigens, and efficiently killed primary human B-NHL samples with variable CD20/CD22 levels. In a patient-derived B-NHL xenograft model, CD20x22 CAR T cells increased overall survival, providing a proof of concept for overcoming resistance mechanisms and offering an option to CD19 targeting.
Contributed by Katherine Turner
ABSTRACT: Despite the remarkable success of autologous chimeric antigen receptor (CAR) T cells, some patients relapse due to tumor antigen escape and low or uneven antigen expression, among other mechanisms. Therapeutic options after relapse are limited, emphasizing the need to optimize current approaches. In addition, there is a need to develop allogeneic "off-the-shelf" therapies from healthy donors that are readily available at the time of treatment decision and can overcome limitations of current autologous approaches. To address both challenges simultaneously, we generated a CD20xCD22 dual allogeneic CAR T cell. Herein, we demonstrate that allogeneic CD20x22 CAR T cells display robust, sustained and dose-dependent activity in vitro and in vivo, while efficiently targeting primary B-cell non-Hodgkin lymphoma (B-NHL) samples with heterogeneous levels of CD22 and CD20. Altogether, we provide preclinical proof-of-concept data for an allogeneic dual CAR T cell to overcome current mechanisms of resistance to CAR T-cell therapies in B-NHL, while providing a potential alternative to CD19 targeting.
Author Info: (1) Cellectis, Inc., New York, New York. (2) Cellectis, SA, Paris, France. (3) Cellectis, Inc., New York, New York. (4) Cellectis, Inc., New York, New York. (5) Cellectis, Inc., Ne
Author Info: (1) Cellectis, Inc., New York, New York. (2) Cellectis, SA, Paris, France. (3) Cellectis, Inc., New York, New York. (4) Cellectis, Inc., New York, New York. (5) Cellectis, Inc., New York, New York. (6) Cellectis, Inc., New York, New York. (7) Cellectis, Inc., New York, New York. (8) Cellectis, Inc., New York, New York. (9) Cellectis, SA, Paris, France. (10) Cellectis, SA, Paris, France. (11) Cellectis, SA, Paris, France. (12) Cellectis, SA, Paris, France.
