Zachary Walsh1, Savannah Ross1, Terry J Fry2. 1. Center for Cancer and Blood Disorders, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, 13123 East 16th Avenue, Box B115, Aurora, CO, 80045, USA. 2. Center for Cancer and Blood Disorders, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, 13123 East 16th Avenue, Box B115, Aurora, CO, 80045, USA. Terry.fry@ucdenver.edu.
Abstract
PURPOSE OF REVIEW: Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable remission induction rates for relapsed/refractory B cell malignancies. However, loss of the CAR-targeted antigen, known as antigen escape, accounts for a substantial percentage of relapses following CAR therapy and is a major barrier to durable remission. Here, we discuss mechanisms for antigen escape and strategies to prevent this pattern of relapse, including the use of multi-specific CARs, which recognize and target multiple tumor-associated antigens simultaneously. RECENT FINDINGS: Preclinical and early clinical trial data indicates that multi-specific CAR therapy for B cell malignancies is both safe and effective. Optimal combinations of target antigens, as well as different multi-specific CAR formats, are currently being evaluated. Although still in early stages of development, multi-specific CAR therapy represents a promising approach to mitigate antigen loss-related relapses and improve durability of remission in patients with refractory B cell malignancies, and may be applicable to other types of cancer.
PURPOSE OF REVIEW: Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable remission induction rates for relapsed/refractory B cell malignancies. However, loss of the CAR-targeted antigen, known as antigen escape, accounts for a substantial percentage of relapses following CAR therapy and is a major barrier to durable remission. Here, we discuss mechanisms for antigen escape and strategies to prevent this pattern of relapse, including the use of multi-specific CARs, which recognize and target multiple tumor-associated antigens simultaneously. RECENT FINDINGS: Preclinical and early clinical trial data indicates that multi-specific CAR therapy for B cell malignancies is both safe and effective. Optimal combinations of target antigens, as well as different multi-specific CAR formats, are currently being evaluated. Although still in early stages of development, multi-specific CAR therapy represents a promising approach to mitigate antigen loss-related relapses and improve durability of remission in patients with refractory B cell malignancies, and may be applicable to other types of cancer.
Entities:
Keywords:
Antigen escape; Antigen loss; Bivalent; CAR T cell; Lineage switch; Multi-specific
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