In a follow-up clinical study, an acute lymphoblastic leukemia (ALL) patient, who experienced multiple relapses of central nervous system leukemia (CNSL) and failed all conventional therapies, was enrolled to receive the CD19-specific 153z CART treatment.
The CD3-CD19 bispecific T-cell-engaging antibody blinatumomab is also the first drug approved in ALL for patients with persistent or recurrent measurable residual disease, providing a new treatment paradigm for these patients.
CARs targeting B cell associated CD19 demonstrated robust in vivo cytolytic activity, expansion, and persistence upon antigen exposure paving the way for clinical application of this technology and ultimately FDA approval for pediatric and young adult acute lymphoblastic leukemia as well as patients with relapsed or refractory diffuse large B cell lymphoma.
We performed a prospective cohort study of clinical manifestations as well as imaging, pathology, CSF, and blood biomarkers on 43 subjects ages 1 to 25 who received CD19-directed CAR/T cells for acute lymphoblastic leukemia (ALL).
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.
A plentitude of durable complete responses using CD19-specific CAR-T cells in patients suffering from various lymphoid malignancies resulted in the approval by the food and drug administration (FDA) of CD19-directed CAR-T cells for the treatment of acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL).
Four relapsed, primary ALLs with CD19 antigen loss obtained after CD19-directed therapy retained BAFF-R expression and activated BAFF-R-CAR, but not CD19-CAR, T cells.
Herein we discuss current approaches incorporating the bispecific T-cell engager blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin (InO), and CD19-directed chimeric antigen receptor T cells in children with relapsed/refractory B-cell ALL and discuss the potential for using these immunotherapies in the treatment of newly diagnosed children.
Anti-CD19 CAR T-cell therapy has revolutionized the treatment of relapsed/refractory pediatric and adult acute lymphoblastic leukemia and refractory adult non-Hodgkin lymphoma, resulting in the expanded use of CAR T cells in multicenter trials and as US FDA-approved products.
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).
With the approval of CD19-targeted CAR T-cells by the Food and Drug Administration in acute lymphoblastic leukemia (ALL) and NHL, this technology is positioned for aggressive expansion to combination therapeutic opportunities and proof of principle towards utility in other malignant disorders.
In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and CD19-targeted CAR T-cells have drastically changed the treatment landscape of B-cell ALL.
Chimeric antigen receptor (CAR) therapy targeting CD19 is an effective treatment for refractory B cell malignancies, especially acute lymphoblastic leukemia (ALL) <sup>1</sup> .
The astonishing clinical success of CD19 chimeric antigen receptor (CAR) T-cell therapy has led to the approval of two second generation chimeric antigen receptors (CARs) for acute lymphoblastic leukemia (ALL) andnon-Hodgkin lymphoma (NHL).
CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting.
Overall, these findings provide important implications for non-viral technology and the proof-of-concept that donor-derived CARCIK-CD19 are indeed effective against relapsed ALL, a possibility that will be tested in Phase I/II clinical trials after allogeneic hematopoietic stem-cell transplantation.
Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects.
Recently, lineage switch to a myeloid phenotype has been described following CD19 targeting treatment in three pediatric patients with mixed lineage leukemia (MLL) rearranged 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.
Adoptive transfer of CD123.CAR or CD19.CAR lymphocytes led to a significant anti-tumor response against acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) disseminated diseases in NSG mice.
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.