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Off-the-shelf CAR-T cells made from a healthy donor, gene-edited to avoid rejection and graft-versus-host disease, produced remission in 14 of 21 patients with relapsed ALL.
This report pooled two phase 1 studies (PALL in 7 children and CALM in 14 adults) of UCART19, allogeneic CD19 CAR-T cells from healthy donors in which TALEN gene editing disrupted the T-cell receptor alpha constant gene (to prevent graft-versus-host disease) and CD52 (to allow alemtuzumab in lymphodepletion). Patients with relapsed or refractory CD19-positive B-cell ALL received fludarabine and cyclophosphamide with or without alemtuzumab followed by UCART19. Complete remission or remission with incomplete count recovery occurred in 14 of 21 patients (67%) at day 28; UCART19 expansion was only seen in patients who received alemtuzumab. Cytokine release syndrome occurred in 91% (grade 3-4 in 3 patients), neurotoxicity in 38% (all grade 1-2), and grade 1 skin graft-versus-host disease in two patients. Most responders proceeded to allogeneic transplant, and durability without transplant was limited.
The UCART19 report was the first clinical evidence that a universal, pre-manufactured CAR-T made from a donor can work, avoiding the weeks of autologous manufacturing and the problem of patients whose own T cells are too damaged. It set the template for later allogeneic programmes (including cemacabtagene autoleucel in the ALPHA studies) and for in vivo CAR generation. Short persistence and the need for deep lymphodepletion remain the central weaknesses.
Shares Allogeneic donor and iPSC master cell banks, Allogeneic (off-the-shelf) cell therapy, Manufacturing cost and time for living and radioactive medicines, CD19.
Shares Point-of-care and decentralised cell manufacturing, Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines, CD19.
Shares ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL, Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines, CD19.
Shares Allogeneic (off-the-shelf) cell therapy, Manufacturing cost and time for living and radioactive medicines, CD19, Acquired resistance to every therapy.
Shares Allogeneic (off-the-shelf) cell therapy, CD19, CAR-T cell therapy, Acute lymphoblastic leukaemia.
Shares In vivo CAR-T, Allogeneic (off-the-shelf) cell therapy, Manufacturing cost and time for living and radioactive medicines, CD19.
Shares ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL, Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines, CD19.
Shares ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL, Cytokine release syndrome (CRS), CD19, CAR-T cell therapy.