AUTHOR=Guo Meng , Sun Chen , Qian Yuping , Zhu Liye , Ta Na , Wang Guangjian , Zheng Jianming , Guo Fengfu , Liu Yanfang 

TITLE=Proliferation of Highly Cytotoxic Human Natural Killer Cells by OX40L Armed NK-92 With Secretory Neoleukin-2/15 for Cancer Immunotherapy

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.632540

DOI=10.3389/fonc.2021.632540

ISSN=2234-943X

ABSTRACT=Adoptive natural killer (NK) cell transfer has been a promising immunotherapy for malignancies, requiring administration sufficient activated cells to ensure treatment effectiveness. However, paucity of clinical grade and low-cost method for large-scale cell expansion limits the feasibility. Here we developed a feeder-based NK cell expansion approach that uses OX40L armed NK-92 cell with secreting neoleukin-2/15 (Neo-2/15), a hyper-stable mimetic with high affinity to IL-2Rβγ. The novel feeder cells (NK92-Neo2/15-OX40L) induce expansion of NK cells with increasing 2180-fold (median; 5 donors; range, 1767 to 2276) after 21 days of co-culture without adding cytokines. These cells were highly cytotoxic against Raji cells and also against several solid tumors in vivo. Mechanistically, NK92-Neo2/15-OX40L induced OX40 and OX40L expression on expanded NK cells and fatherly promoted OX40-OX40L positive feedback loop, which promoting NK cell function. Our data provided a novel NK cell expansion methodology and mechanistic insights into OX40-OX40L axis regulating NK cell expansion.