Chimeric antigen receptor (CAR) T cells have hit prime time, with the 2 recent FDA approvals for this class of cell-based therapy. Undoubtedly this option will be a game changer for patients with B-cell malignancies who have only a small number of available treatment options; however, questions regarding the real-world utility of CAR T-cell therapies remain. Several challenges may affect the adoption of CAR T-cell therapy, which range from logistical complexities of therapeutic development to the potentially fatal toxicities of treatment.
A number of innovations are already entering the scene, including next-generation “armored” CARs and the application of state-of-the-art genome-editing technologies.
Harnessing Antitumor Immune Cells
CAR T-cell therapy falls under the banner of adoptive cellular therapy (ACT), in which the effector cells of the immune system, predominantly the T cells, are transplanted into a patient. The graft-versus-tumor effect observed in patients undergoing allogeneic hematopoietic stem cell transplantation served as the stimulus for pursuing ACT. T cells present in the transplanted material were seemingly capable of mounting an effective antitumor immune response, but this was limited by the development of graft-versus-host disease (GVHD), wherein the transplanted T cells also attacked healthy tissue, causing severe toxicity.
Figure. Mechanism of Action of CAR Therapies
The CAR T-Cell Race to the Market
In this rapidly evolving field of immuno-oncolytic therapeutic development, the most clinically advanced CAR T cells are currently those engineered against CD19, a cell surface receptor constitutively expressed on tumors in hematologic malignancies. Several pharmaceutical companies raced to be the first to secure regulatory approval, but ultimately the first-to-market advantage went to Novartis’ tisagenlecleucel (Kymriah).
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