Control of graft-versus-host disease with rabbit anti-thymocyte globulin, rituximab, and bortezomib in TCRαβ/CD19-depleted graft transplantation for leukemia in children: a single-center retrospective analysis of two GVHD-prophylaxis regimens.
The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models.
We performed a preclinical validation using a model of CD33<sup>+</sup> AML, and generated iC9 CAR T-cells co-expressing a CAR targeting the AML-associated antigen CD33 and a selectable marker (ΔCD19).ΔCD19 selected (sel.) iC9-CAR.CD33 T-cells were effective in controlling leukemia growth in vitro, and could be partially eliminated (76%) using a chemical inducer of dimerization that activates iC9.
In this regard, CD19-specific CAR T cell therapies have achieved dramatic objective responses for a high percent of patients with CD19-positive leukemia or lymphoma.
These results are the first to establish the clinical activity of a CD22-CAR in B-ALL, including leukemia resistant to anti-CD19 immunotherapy, demonstrating potency against B-ALL comparable to that of CD19-CAR at biologically active doses.
We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19<sup>-</sup> leukemia that aberrantly expressed the anti-CD19 CAR.
The clinical use of genetically modified T-cell therapies has led to unprecedented response rates in leukemia and lymphoma patients treated with anti-CD19 chimeric antigen receptor (CAR)-T. Despite this clinical success, FDA-approved T-cell therapies are currently limited to B-cell malignancies, and challenges remain with managing cytokine-related toxicities.
The remarkable clinical response rates achieved by adoptive transfer of T cells that target CD19 in patients with leukemia and lymphoma have led to a growing number of clinical trials exploring CAR T-cell therapy for solid tumors.
During this treatment, the leukemia lost CD19 expression as well as nearly all other B-cell markers, while still harboring the initial minimal residual disease marker, and switched to a myeloid phenotype.
The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients, with a realistic hope for cure.
We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM-ALL).
Novel therapies with chimeric antigen receptor (CAR)-transduced T cells (TCs) sparked new hope for patients with relapsed or refractory CD19-positive leukemia or lymphoma even after stem cell therapies.
Infusion of CD19-ENG T cells resulted in regression of leukemia or lymphoma in xenograft models and a survival advantage in comparison to control mice.
In this study, we compared CD19 bispecific T-cell engager (BiTE)-transferred T cells that had been transfected by RNA electroporation with CD19 CAR RNA-transferred T cells both in vitro and in an aggressive Nalm6 leukemia mouse model.