Anti-CD137 agonistic mAb increases rituximab-mediated NK-cell cytotoxicity on tumor cells. NK cells isolated and purified from the peripheral blood of healthy donors were analyzed for degranulation by CD107a mobilization after 24-hour culture in 5 conditions: medium alone; CD20⁺ lymphoma cell line (Raji, Ramos, DHL-4); tumor and rituximab; tumor and anti-CD137 antibody; or tumor, rituximab, and anti-CD137 agonistic antibody. (A) Raji, *P = .01. (B) Ramos, *P = .003. (C) DHL-4, *P = .002. A representative flow cytometric plot of CD107a expression with Ramos target cells is shown in supplemental Figure 3. NK-cell cytotoxicity on Raji, Ramos, and DHL-4 tumor cells was analyzed in a chromium-release assay (D-F). Preactivated NK cells (as described in “Methods”) were purified before being incubated with chromium-labeled Raji, Ramos, and DHL-4 cells for 4 hours. (D-F) Percent lysis of target cells by chromium release at varying effector (activated NK cells)-to-target (Raji) cell ratios cultured with medium alone (♦), anti-CD137 (▴), rituximab (●), or rituximab and anti-CD137(■) antibodies. (D) Raji, *P = .01. (E) Ramos, *P = .01. (F) DHL-4, *P = .009.