The prognosis is very dismal for patients with relapsed CD20+ B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcome in patients with recurrent/refractory CD20+ B-NHL. In this study, we investigated functional activities of anti-CD20 CAR-modified, expanded peripheral blood NK cells (exPBNK) following mRNA nucleofection against CD20+ B-NHL in vitro and in vivo. CAR+ exPBNK had significantly enhanced in vitro cytotoxicity compared to CAR- exPBNK against CD20+ Ramos (p<0.05), Daudi, Raji, and two rituximab-resistant cell lines: Raji-2R and Raji-4RH (p<0.001). As expected, there was no significant difference against CD20- RS4;11 and Jurkat cells. CD107a degranulation and intracellular IFNγ production was also enhanced in CAR+ exPBNK in response to CD20+ B-NHL-specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NSG mice, the luciferase signals measured in the CAR+ exPBNK-treated group were significantly reduced compared to the signals measured in the untreated mice and in mice treated with the CAR- exPBNK. Furthermore, the CAR exPBNK-treated mice had significantly extended survival time (p<0.001) and reduced tumor size compared to those of the untreated and the CAR- exPBNK-treated mice (p<0.05). These preclinical data suggest that ex vivo-expanded PBNK cells modified with anti-CD20 CAR may have therapeutic potential for treating patients with poor risk CD20+ hematological malignancies.
- Received June 12, 2014.
- Revision received November 22, 2014.
- Accepted November 25, 2014.
- Copyright © 2014, American Association for Cancer Research.