Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis

• Co-treatment with anti-CD19 antibody induces rapid detachment of anti-CD19 CAR-NK/-T cells from target cells, mitigating trogocytosis.

• Combined therapy with anti-CD19 antibody enhances antitumor activity of anti-CD19 CAR-NK and -T cells both in vitro and in vivo.

Anti-CD19 chimeric antigen receptor (CAR)-engineered T and NK cell therapies have revolutionized the treatment of B cell malignancies, but challenges including CD19 antigen loss greatly hinder their full therapeutic potential. Here we demonstrated that co-treatment with anti-CD19 monoclonal antibody enhances antitumor activity of anti-CD19 CAR-T and -NK cells. Even though the treated antibody interferes with CD19 antigen binding of CAR, it significantly induces rapid detachment of anti-CD19 CAR effector cells from target cells, facilitating improved serial killing. This reduced interaction between CAR effector cells and target cells also leads to the alleviation of CAR-mediated trogocytosis. Interestingly, co-treatment with anti-CD19 antibody reveals time-dependent effects on the antitumor activity of anti-CD19 CAR-T cells, characterized by a reduction in early T cell activation followed by sustained high activity during prolonged exposure to target cells. This temporal modulation ultimately results in enhanced antitumor potency in vivo. These findings underscore the improved therapeutic efficacy achieved by combining anti-CD19 antibody with anti-CD19 CAR-T or -NK cells against B cell malignancies.