Background: CAR-T (Chimeric Antigen Receptor T-Cell) therapy has proven to be highly effective in the treatment of oncohematological diseases. In pivotal clinical trials for CD19-positive tumors (ZUMA-1, ZUMA-3, JULIET, TRANSCEND), complete response rates were 58%, 51%, 40%, and 59%, respectively. However, the success of CAR-T therapy is limited by two major unresolved challenges: acute side effects and cancer recurrence. To prevent recurrence, strategies are being developed to modify the CAR construct and enhance the expansion and persistence of CAR-T cells in the body. Since recurrences often occur due to loss of target antigen expression by tumor cells, targeting two or more tumor antigens may significantly reduce recurrence rates. Aim of the study: This review compiles and analyzes results from clinical trials of bispecific CAR-T therapies and compares key clinical response rates of promising CAR-T candidates with those of approved CAR-T therapies. Materials and methods: Relevant literature was reviewed using PubMed, Scopus, Web of Science, and ClinicalTrials.gov databases. Results: The limited number of clinical trials did not allow for identification of significant differences in primary outcomes of CAR-T therapy. Nevertheless, a trend toward increased relapse-free survival was observed in patients treated with bispecific CAR-T variants compared to monospecific therapies. Recurrence-free survival rates ranged from 61% to 90% for CD19/CD20-targeted therapies, 40% to 85% for CD19/CD22-targeted therapies, and 44% to 61% for monospecific anti-CD19 CAR-T therapy. Conclusion: Cancer recurrence after CAR-T therapy is frequently associated with antigen loss by tumor cells. Clinical trial results suggest that targeting two or more antigens with CAR-T therapies may be an effective approach to reduce recurrence risk without increasing immune or neurotoxicity
Background: CAR-T (Chimeric Antigen Receptor T-Cell) therapy has proven to be highly effective in the treatment of oncohematological diseases. In pivotal clinical trials for CD19-positive tumors (ZUMA-1, ZUMA-3, JULIET, TRANSCEND), complete response rates were 58%, 51%, 40%, and 59%, respectively. However, the success of CAR-T therapy is limited by two major unresolved challenges: acute side effects and cancer recurrence. To prevent recurrence, strategies are being developed to modify the CAR construct and enhance the expansion and persistence of CAR-T cells in the body. Since recurrences often occur due to loss of target antigen expression by tumor cells, targeting two or more tumor antigens may significantly reduce recurrence rates. Aim of the study: This review compiles and analyzes results from clinical trials of bispecific CAR-T therapies and compares key clinical response rates of promising CAR-T candidates with those of approved CAR-T therapies. Materials and methods: Relevant literature was reviewed using PubMed, Scopus, Web of Science, and ClinicalTrials.gov databases. Results: The limited number of clinical trials did not allow for identification of significant differences in primary outcomes of CAR-T therapy. Nevertheless, a trend toward increased relapse-free survival was observed in patients treated with bispecific CAR-T variants compared to monospecific therapies. Recurrence-free survival rates ranged from 61% to 90% for CD19/CD20-targeted therapies, 40% to 85% for CD19/CD22-targeted therapies, and 44% to 61% for monospecific anti-CD19 CAR-T therapy. Conclusion: Cancer recurrence after CAR-T therapy is frequently associated with antigen loss by tumor cells. Clinical trial results suggest that targeting two or more antigens with CAR-T therapies may be an effective approach to reduce recurrence risk without increasing immune or neurotoxicity
The work was carried out within the framework of the Strategic Academic Leadership Programme (PRIORITY-2030) of Kazan Federal University