CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell lymphomas

Abstract

Ubiquitous expression of CD19 on B cell non-Hodgkin lymphoma identified it as a potential target for immune-based therapies. Areas covered: This article reviews the current literature on anti-CD19 therapies currently in clinical trials including monoclonal antibodies (mAb), antibody targeted cytotoxic drug conjugates (ADC), bispecific antibodies, and chimeric antigen receptor (CAR) modified T cells. Expert opinion: Naked anti-CD19 mAbs have shown little clinical benefit in B cell lymphomas. Despite unusual toxicity profiles with many anti-CD19 ADCs slowing development, durable remissions in a substantial minority of patients with refractory aggressive lymphomas should encourage continued efforts in this area. Blinatumomab, an anti-CD19 bispecific T cell engager, has shown impressive responses in relapse/refractory diffuse large B cell lymphoma (DLBCL), but is plagued by neurotoxicity issues and the need for continuous infusion. CD19 targeting CAR-T cell therapies are the most promising, with the potential for curing a third of refractory DLBCL patients. There is still much work to be done to address potentially life-threatening cytokine release syndrome and neurotoxicity, an extended production time precluding patients with rapidly progressive disease, and treatment expense. However, if the promise of CAR-T cell technology is confirmed, this will likely change the approach and prognosis for relapse/refractory aggressive lymphoma.

Molecular analysis of a CD19-negative diffuse large B-cell lymphoma

“…6 Of note, CD19 has become a therapeutic target for bispecific antibodies (blinatumomab) or chimeric antigen receptor (CAR) T cells in B-cell malignancies. 7 We report the case of a patient diagnosed with diffuse large B-cell lymphoma (DLBCL) that did not express CD19 as assessed by flow cytometry and describe the molecular mechanisms that explain this exceptional observation.…”

Identification of major depressive disorder disease-related genes and functional pathways based on system dynamic changes of network connectivity

“…Another crucial gene, CD19, is a B cell-speci c member of the immunoglobulin superfamily expressed by pre-B cells from the time of heavy chain rearrangement to nal differentiation into plasma cells. By regulating B cell receptor signaling, CD19 guides the fate of B cells and differentiation lymphopoesis (45). In our study, CD19 is the top gene in the T cell receptor signaling pathway that participate in immune regulation and in ammatory response.…”

Dendritic cell/cytokine‐induced killer cell‐based immunotherapy in lung cancer: What we know and future landscape

“…These T cells were called CAR‐T cell. CAR‐T cell therapies targeted the CD19 antigen was approved by FDA for B‐cell lymphoma (Watkins & Bartlett, ). The genetic modifications that occur with retroviral vectors in patients’ T cells, after a while may appear dangerous in the patients.…”