NYMC Faculty Publications
Targeting CD20+ Aggressive B-Cell Non-Hodgkin Lymphoma by Anti-CD20 CAR Mrna-Modified Expanded Natural Killer Cells in Vitro and in NSG Mice
Author Type(s)
Faculty
DOI
10.1158/2326-6066.CIR-14-0114
Journal Title
Cancer Immunology Research
First Page
333
Last Page
44
Document Type
Article
Publication Date
4-1-2015
Abstract
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 outcomes 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 with 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 were also enhanced in CAR(+) exPBNK in response to CD20(+) B-NHL -: specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NOD/SCID/γ-chain(-/-) (NSG) mice, the luciferase signals measured in the CAR(+) exPBNK-treated group were significantly reduced, compared with 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 with those of the untreated and the CAR(-) exPBNK-treated mice (P < 0.05). These preclinical data suggest that ex vivo-exPBNK modified with anti-CD20 CAR may have therapeutic potential for treating patients with poor-risk CD20(+) hematologic malignancies.
Recommended Citation
Chu, Y., Hochberg, J., Yahr, A., Ayello, J., van de Ven, C., Barth, M., Czuczman, M., & Cairo, M. S. (2015). Targeting CD20+ Aggressive B-Cell Non-Hodgkin Lymphoma by Anti-CD20 CAR Mrna-Modified Expanded Natural Killer Cells in Vitro and in NSG Mice. Cancer Immunology Research, 3 (4), 333-44. https://doi.org/10.1158/2326-6066.CIR-14-0114