Since the FDA-approval of tisagenlecleucel (KymriahTM, Novartis) in August 2017 to treat acute lymphoblastic leukemia (ALL), ongoing investigations rev’d up and new ones initiated leading up to further approval of axicabtagene ciloleucel (YescartaTM, Kite Pharma) for the treatment of relapsed or refractory large B-cell lymphoma 2 months later.
Albeit major credit for utilizing chimeric antigen receptor (CAR) T cells will remain with Dr. Carl June and his team at Penn, it is important to continue to acknowledge and render due credit to the scientist from St Jude’s who first developed this specific CAR that Dr. June later utilized to cure Emily Whitehead and others. With its FDA approval for select ALL and B-cell lymphoma patients, CAR-T cells will likely be tried across a myriad of medical illnesses—malignant, autoimmune, and infections, leading to significant research funding becoming available [1, 2].
As the technique gets widely investigated and gets ready to take various shapes, identifying heterogeneous proteins targeting diverse cancer cells, I bring the attention to the original creator of CD19+ CAR that was initially designed with an intention to treat ALL patients. Dr. Dario Campana, along with Dr. Chihaya Imai, from St Jude’s Children’s Research Hospital in Tennessee, first published his CAR design in Leukemia in 2004 . The addition of co-stimulatory signal, 41-BB (or CD137), to the chimeric receptors significantly improved their function and made clinical responses durable.
As we all work as a team and progress toward finding cancer cures, it would be inspirational to know and remember each member’s contribution toward alleviating sufferings of cancer patients, such as Emily.
Rosenbaum L. Tragedy, perseverance, and chance—the story of CAR-T therapy. N Engl J Med 2017;377:1313–5.
Kuehn BM. The promise and challenges of CAR-T gene therapy. JAMA 2017;318:2167–9.
Imai C, Mihara K, Andreansky M, Nicholson IC, Pui CH, Geiger TL, et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia. 2004;18:676–84.
Conflict of interest
The authors declare that they have no conflict of interest.
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Abid, M.B. The revving up of CARs. Gene Ther 25, 162 (2018). https://doi.org/10.1038/s41434-018-0015-x
World Journal of Gastroenterology (2020)
Journal for ImmunoTherapy of Cancer (2019)
Experimental Hematology & Oncology (2019)