Anti-CD19 CAR-T cells: Digging in the dark side of the golden therapy. (January 2021)

• Record Type: Journal Article
• Authors: Bouziana, Stella; Bouzianas, Dimitrios
• Is Part Of: Critical reviews in oncology/hematology. Volume 157(2021)
• Publication Date: 2021-01
• Subjects: CAR-T cells -- Acute lymphoblastic leukemia -- Non-Hodgkin lymphoma -- Resistance mechanisms -- Relapse -- Antigen escape; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2020.103096
• Languages: English
• ISSNs: 1040-8428

Abstract

Graphical abstract: Highlights: In hematological malignancies a significant proportion of initially responded patients finally relapse after anti-CD19 CAR-T cell therapy. The phenomenon of subsequent relapses after anti-CD19 CAR-T cell therapy implies the presence of resistance mechanisms. A complexity of limitations and resistance mechanisms to CAR-T cells are implicated in both antigen-positive and antigen-negative relapses. Future advances in CAR-T cell technology could render CAR-T cells a safe and potentially curative treatment for hematological malignancies. Abstract: The unprecedented technological advances in genetic engineering have resulted in the advent of the very promising chimeric antigen receptor (CAR)-T cell therapy. Based on the striking outcomes of clinical trials, the first two commercial CAR-T cell products, tisagenlecleucel and axicabtagene ciloleucel, have been approved in both the United States and Europe for the treatment of patients with highly aggressive CD19-positive hematological malignancies. Despite the initial remarkable responses many patients finally relapse, implying the presence of resistance mechanisms. In this review, we describe the limitations and resistance mechanisms to anti-CD19 CAR-T cells and address potential strategies to overcome CAR-T cell barriers.