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.
The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models.
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.
T cells genetically engineered to express chimeric antigen receptors (CAR) constitute the most clinically advanced form of ACT approved to date for the treatment of CD19-positive leukaemias and lymphomas.
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.
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.
Human CD19 antigen is a 95-kDa type I membrane glycoprotein in the immunoglobulin superfamily whose expression is limited to the various stages of B-cell development and differentiation and is maintained in the majority of B-cell malignancies, including leukemias and non-Hodgkin lymphomas of B-cell origin.
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.
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).
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 targeting of CD19, a cell surface molecule expressed in the vast majority of leukemias and lymphomas, has been successfully translated in the clinic, earning CAR therapy a special distinction in the selection of "cancer immunotherapy" by Science as the breakthrough of the year in 2013.
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.
Although donor-derived CD19-directed chimeric antigen receptor-modified (CAR) T cells can potentially cure leukaemia, their effectiveness and safety have not been confirmed in relapsed B-ALL cases after haplo-HSCT.