Multiple doses of hnCD16-iNK cells effectively mediate improved ADCC in vivo against B-cell lymphoma. (A) Schema of multiple NK cell dosing study. NSG mice were inoculated intraperitoneally with 2 × 10⁵ Luc-expressing Raji cells, and tumor engraftment was assessed by IVIS imaging 3 days later for a baseline pretreatment reading. On day 4 after transplant, mice were left untreated or were treated with 1 × 10⁷ PB-NK cells or hnCD16-iNK cells, alone or in combination with 300 μg of rituximab weekly for 4 weeks. NK cells were supported by injection of IL-15 for the first week and by injection of IL-2 for 3 weeks. IVIS imaging was done weekly to monitor tumor progression. (B) Tumor burden was determined by BLI over the first 28 days. (C) Time course of IVIS imaging. Data are mean ± SEM for the mice in panel B. Anti-CD20 vs PB-NK+anti-CD20 not significant for all data points, 2-tailed Student t test. (D) Kaplan-Meier curve representing the percent survival of the experimental groups. The median survival for the untreated group and the groups treated with Anti-CD20, PB-NK+anti-CD20, and hnCD16-iNK+anti-CD20 are 25, 47, 61, and 76 days, respectively. Anti-CD20 vs PB-NK+anti-CD20, P = .0185; anti-CD20 vs hnCD16-iNK+anti-CD20, P = .0065; PB-NK+anti-CD20 vs hnCD16-iNK+anti-CD20, P = .0485; 2-tailed log-rank test. *P < .05, **P < .01, anti-CD20 vs hnCD16-iNK+anti-CD20, 2-tailed Student t test.