T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial

Abstract

National Institutes of Health Intramural funds and St Baldrick's Foundation.

Perspectives of Fc engineered antibodies in CD19 targeting immunotherapies in pediatric B-cell precursor acute lymphoblastic leukemia

“…2 Impressively, in a phase I study by Lee and colleagues in children and younger adults with BCP-ALL CD19 CAR T cell therapy achieved a complete response in 70% of patients. 23 In another pilot trial in relapsed/refractory childhood ALL, CR was observed in 94% of the patients and the OS rate was 78%. 25 Two CD19 CAR T cell therapies have recently been approved by the FDA.…”

“…1A). 2 , 23-24 For generation of autologous CAR T cells, T cells are isolated, expanded ex vivo, and transduced with the CD19 specific CAR construct using viral transduction methods, and re-infused into the patient. Costimulatory domains included in the CAR were shown to be necessary to achieve CAR T cell expansion in the patient and for long persistence, which provides ongoing control of the disease.…”

“…23 , 25 , 30 CD19-negative relapses were observed both during blinatumomab and CAR T cell treatment. In the majority of cases CD19 antigen loss was attributed to a selection of leukemic cells expressing either CD19 isoforms that lack the cognate epitope for the CD19 CAR construct or CD19 isoforms that were not shuttled to the cell surface.…”

Recent advances in T‐cell immunotherapy for haematological malignancies

“…(Sadelain 2015) Several groups have reported CR rates as high as 90% in ALL after administration of a single dose of CD19-CAR T-cells following lymphodepleting chemotherapy, even in heavily pre-treated children and adults. (Davila et al 2014, Lee et al 2015, Maude et al 2014) The success of CD19-specific T-cells in early phase trials has resulted in the designation of “FDA breakthrough status” and commercialization efforts. (June et al 2015, Sadelain 2015) There are currently 45 actively enrolling clinical trials targeting CD19 with CAR T-cells.…”

“…(Rooney et al 2014, Sadelain 2015, Vonderheide and June 2014) Indeed, this is an exciting time in the field of T-cell immunotherapy with in vitro discoveries paving the way for bench-to-bedside translation and resulting in remarkable clinical responses in a variety of haematological malignancies. In particular, adoptively transferred T-cells genetically modified to express CD19 CARs have shown great promise (Davila et al 2014, Lee et al 2015, Maude et al 2014), although some haematological malignancies remain recalcitrant. For these tumours, combination immunotherapeutic approaches are being investigated and may prove beneficial.…”