2017: First CAR-T Approved (Kymriah) (2017)
On 30 August 2017, the FDA approved tisagenlecleucel (Kymriah, Novartis) for the treatment of
patients up to 25 years of age with relapsed or refractory B-cell precursor acute lymphoblastic
leukaemia (ALL)—making it the first CAR-T cell therapy and the first gene therapy for cancer
approved in the United States. The approval was based on the ELIANA trial, a global single-arm
study that demonstrated an overall remission rate of 81 % in paediatric and young adult patients
who had previously exhausted all standard treatment options including multiple chemotherapy
regimens and, in many cases, stem-cell transplantation.
Tisagenlecleucel encodes a 4-1BB co-stimulated CAR targeting CD19, the pan-B-cell antigen
expressed on malignant B-lymphoblasts. The lentiviral vector, manufactured at the University of
Pennsylvania's clinical cell and vaccine production facility and later scaled by Novartis, transduces
the patient's own T cells ex vivo; the engineered product is shipped back to the infusing centre
and administered as a single infusion following lymphodepleting chemotherapy. The 4-1BB
co-stimulation domain—developed in Michel Sadelain's laboratory—promotes superior T-cell
persistence compared with CD28-based designs, contributing to durable responses.
The FDA approval created a new regulatory pathway for autologous gene-modified cell therapies and
established the biologics license application (BLA) framework for CAR-T products. The agency
simultaneously approved a risk evaluation and mitigation strategy (REMS) requiring certified
treatment centres equipped to recognise and manage cytokine release syndrome (CRS) and
immune effector cell-associated neurotoxicity syndrome (ICANS) with tocilizumab and corticosteroids.
Axicabtagene ciloleucel (Yescarta, Kite/Gilead) received approval one month later for adult
diffuse large B-cell lymphoma, and the CAR-T pipeline rapidly expanded to multiple myeloma,
mantle cell lymphoma, follicular lymphoma, and—through allogeneic and next-generation platforms—
toward solid tumours.
Bu Neden Önemliydi
Kymriah's approval established CAR-T cell therapy as a commercial medical product, creating the
first approved gene therapy for cancer and demonstrating that a personalised, patient-derived living
drug could achieve previously unattainable remission rates in haematological malignancies. It opened
the regulatory, manufacturing, and clinical management infrastructure that underpins all subsequent
cell and gene therapy oncology products.