Enthusiasm with results of early phase trials using chimeric-antigen-receptor (CAR)-T cells targeting CD19 have led to fast approval of this novel immunotherapy for the treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma, and to an explosion of clinical trials with such cells.
Tisagenlecleucel, a CD19-specific autologous chimeric antigen receptor (CAR)-T cell therapy, is efficacious for the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
Following FDA approval of CAR T cells directed against the CD19 protein for the treatment of acute lymphoblastic leukemia and diffuse large B cell lymphoma, CAR T cells are poised to enter mainstream oncology.
This resulted in two recent FDA approvals of CAR T cells directed against the CD19 protein for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
Clinical results have demonstrated efficacious responses in patients with the CD19 positive diseases B cell acute lymphoblastic leukemia and diffuse large B cell lymphoma.
Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants.
As a result of complete and durable responses in individuals who are refractory to standard of care therapy, CAR T cells directed against the CD19 protein have been granted United States Food and Drug Administration (FDA) approval as a therapy for treatment of pediatric and young adult acute lymphoblastic leukemia and diffuse large B cell lymphoma.
We used autologous T cells that express a CD19-directed CAR (CTL019) to treat patients with diffuse large B-cell lymphoma or follicular lymphoma that had relapsed or was refractory to previous treatments.
According to an interim analysis of phase II data from a study of the anti-CD19 chimeric antigen receptor T-cell therapy KTE-C19, 76% of 51 patients with diffuse large B-cell lymphoma responded to the treatment; 47% had a complete response.
The ratio of FOXP1L:FOXP1S isoforms correlated with differential expression of plasmacytic differentiation markers in U-2932 subpopulations, and altering this ratio was sufficient to modulate CD19 expression in diffuse large B-cell lymphoma cell lines.
Moreover, we detected a similarly functioning prosurvival pathway involving phosphorylated CD19 and PI3K-dependent Erk phosphorylation in human diffuse large B-cell lymphoma cell lines.