The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8<sup>+</sup> T cells and natural killer (NK) cells, in the bone marrow.
In comparison with the children, we showed that alternatively spliced CD19 mRNA isoforms affecting exon 2 are also expressed in 6 adult patients with CD19B-ALL.
The CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has been widely proved effective on relapsed and refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL).
A dual inhibitor of PI3K and mTOR, PI-103, was more effective than rapamycin at suppressing proliferation of mouse pre-B-ALL and human CD19+CD34+)Ph+ ALL leukemia cells treated with the ABL kinase inhibitor imatinib.
Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).
Thirty-seven of them were common-ALL positive for CD10 "common-ALL antigen (CALLA)" (NL-1), CD19(B4) and HLA-DR. One was pre-B ALLnegative for CALLA and another null-ALL which expressed HLA-DR alone.
Acquisition of anti-CD19 CARs via trogocytosis enhanced NK cell-mediated cytotoxicity against the B-cell acute lymphoblastic leukemia (B-ALL) cell lines and primary B-ALL cells derived from patients.
At the time of failure, among 61 patients evaluated for immunophenotype, 56 (92%) had CD19-positive blasts; only five (8%) had ALL recurrence with CD19-negative disease.
Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication.
PB-derived CAR(+) CTLs produced interferon-gamma (IFNgamma) in response to cytomegalovirus-pp65, adenovirus-hexon, and Epstein-Barr virus pepmixes (from 205 +/- 104 to 1034 +/- 304 spot-forming cells [SFCs]/10(5) T cells) and lysed primary B-ALL blasts in (51)Cr-release assays (mean, 66% +/- 5% specific lysis; effector-target [E/T] ratio, 40:1) and the CD19(+) Raji cell line (mean, 78% +/- 17%) in contrast to nontransduced controls (8% +/- 8% and 3% +/- 2%).
To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL.
The bone marrow was markedly hypercellular with a total infiltration of agranular lymphoid blast cells with a B-II (pre-B) lymphoblastic phenotype: cyCD79α(+), CD19(+), sCD22(+), CD10(+), CD20(-), CD34(+), and sIgM(-), with dim aberrant co-expression of the myeloid-associated markers CD13(+) and CD33(+).
A 10-year-old boy with B-ALL who never achieved minimal residual disease (MRD) negative status after 5 courses of chemotherapy was enrolled into our study and received a total of 3.19×10/kg autologous CD19 CAR-T-cells.
Since CD19 negative B-ALL are extremely rare, we report three cases of B-ALL with negative expression of CD19 and discussed its implication in the diagnosis, residual disease monitoring and future targeted therapy.
We previously described a mechanism of acquired resistance of B-cell acute lymphoblastic leukemia to CD19-directed chimeric antigen receptor T-cell (CART) immunotherapy.
The bulk of clinical data available is on CD19-targeting CAR T cells for the treatment of B-cell acute lymphocytic leukemia (B-ALL), chronic lymphocytic leukemia, and B-cell non-Hodgkin lymphoma.
These anti-CD19 chimeric antigen receptor-T cells (CAR) proved to be highly effective in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and specific histologic subtypes of B-cell non-Hodgkin lymphomas.