The advent of CD19-specific chimeric antigen receptor (CAR) T cells has proven to be a powerful asset in the arsenal of cancer immunotherapy of acute lymphoblastic leukemia and certain B cell lymphomas.
Immunotherapy with the adoptive transfer of T cells redirected with CD19-specific chimeric antigen receptors (CARs) for B-lineage acute lymphoblastic leukemia (ALL) can salvage >80% of patients having relapsed/refractory disease.
Thus, the cell type-specific cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19 heteroconjugate.
Areas covered: Recently, the Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell product, tisagenlecleucel, for the treatment of pediatric and young adult patients with relapsed/refractory ALL.
The anti-CD19 immunotoxin (IT) (HD37-dgRTA) is effective in killing B-lineage leukemia cells and in curing severe combined immunodeficient mice with acute lymphoblastic leukemia.
The observed in vitro and in vivo anti-leukemic potency of the αCD19-AON immunoconjugate provides the first preclinical proof-of-principle that t(1;19)(+) high risk B-lineage ALL can be treated with leukemia-specific biotherapeutic agents that knock-down E2A-PBX1 expression.
We infused autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at doses of 0.76×10(6) to 20.6×10(6) CTL019 cells per kilogram of body weight.
We demonstrate that CD19-tPSMA<sup>(N9del)</sup> CAR T cells can be tracked with [<sup>18</sup>F]DCFPyL PET in a Nalm6 model of acute lymphoblastic leukemia.
Four hematological groups could be distinguished: (i) 13 cases of acute lymphoblastic leukemia (ALL) of B lineage, mostly CD19+; (ii) eight cases of biphenotypic leukemia: CD19+ (most often) ALL but with simultaneous or inducible expression of differentiation marker of monocytic lineage.
In this study, we sought to maximize the antileukemic activity of anti-CD19 receptor-modified CIK cells against B-lineage acute lymphoblastic leukemia (ALL).
The CD19/CD3-bispecific T cell-engaging (BiTE®) monoclonal antibody blinatumomab can transiently bind cytotoxic T cells to CD19<sup>+</sup> target B cells of ALL inducing their serial lysis.
ACT based on the administration of cytotoxic T cells genetically engineered to express a chimeric antigen receptor (CAR) recognizing CD19 expressed by B cell malignancies has been shown to induce complete lasting responses in patients with chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL).
On the basis of promising preclinical data demonstrating the eradication of systemic B-cell malignancies by CD19-targeted T lymphocytes in vivo in severe combined immunodeficient-beige mouse models, we are launching phase I clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia.
Chimeric antigen receptor T cells (CAR-T) with anti-CD19 have shown great promise in the treatment of relapsed and refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL).
Quantitative analysis of L3 in 12 infants and 91 older children with non-T ALL indicated lack of expression of polypeptide L3 in leukemic cells of infants which, in most cases, expressed HLA-DR and CD19 and lacked CD10.
Here we show that directing a CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia.
Current, up-to-date published studies on anti-CD19 CAR therapy for acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) with observed side effects are discussed and an outlook on 58 ongoing trials is given.
A newly established human leukemia cell line, OM9;22, is reported, with B-precursor immunophenotype (CD10+ CD19+ CD22+ HLA- DR+ C mu-) and CD13 antigen, originated from a 19-year-old female patient with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL).
Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor-modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia.
Extramedullary relapse and discordant CD19 expression between bone marrow and extramedullary sites in relapsed acute lymphoblastic leukemia after blinatumomab treatment.
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.
Recent clinical trials of chimeric antigen receptor (CAR) T cells directed toward CD19 as a stand-alone therapy have shown sustained complete responses in patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia.
We determined the expression of LTB using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) on a series of RNA samples from CD3(+) T cells and CD19(+) B cells isolated from peripheral blood (n=7); CD19(+) B cells isolated from lymph nodes (n=11) and from patients with acute lymphoblastic leukemia (ALL; n=16), acute myeloid leukemia (AML; n=43), chronic myeloid leukemia (CML; n=12), mantle cell lymphoma (MCL; n=19), chronic lymphocytic leukemia (CLL; n=32) and small lymphocytic lymphoma (SLL; n=22).