Abstract
Chimeric antigen receptor (CAR) modified T cell therapy has revolutionized the treatment of relapsed and refractory hematological malignancies. Through targeting of the CD19 antigen on B cells durable remissions have been achieved in patients with B cell non-Hodgkin lymphoma and acute lymphoblastic lymphoma. Despite impressive responses, multiple escape mechanisms to evade CAR-T cell therapy have been identified, among which the most common is loss of the target antigen. In this review we will highlight outcomes to date with CD19 CAR-T cell therapy, describe the current limitations of single targeted CAR-T therapies, review identified tumor escape mechanisms, and lastly discuss novel strategies to overcome resistance via multi-targeted CAR-T cells.
Highlights
Adoptive cell transfer utilizing autologous T cells genetically engineered ex vivo to target tumor antigens has revolutionized the treatment of relapsed, refractory hematological malignancies
This vector does not target more than one antigen receptor, the idea is that the armored chimeric antigen receptor (CAR)-T cells might be able to prevent antigen escape by providing a more vigorous initial response that would eliminate the malignant cells before antigen escape develops
CD19 CAR-T cell treatments have transformed the management of B cell hematological malignancies
Summary
Adoptive cell transfer utilizing autologous T cells genetically engineered ex vivo to target tumor antigens has revolutionized the treatment of relapsed, refractory hematological malignancies. These preclinical findings were translated into a Phase 1, first-in-human bispecific CAR-T cell trial with an anti-CD19/anti-CD20 tandem receptor (NCT03019055) Results from this dose-escalation study demonstrated an ongoing complete response (CR) or partial response (PR) in 3/6 heavily pre-treated and relapsed B cell NHL patients treated with CAR-20.19-T cells. This vector does not target more than one antigen receptor, the idea is that the armored CAR-T cells might be able to prevent antigen escape by providing a more vigorous initial response that would eliminate the malignant cells before antigen escape develops
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