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

Frontiers in Oncology

Chen Sun¹  Guangjian Wang¹  Jianming Zheng²  Yuping Qian²  Liye Zhu²  Fengfu Guo³  Yanfang Liu³  Meng Guo⁴  Na Ta⁴ 

[1] Institute of Immunology, Navy Medical University, Shanghai, China;Department of Pathology, Changhai Hospital, Navy Medical University, Shanghai, China;Department of Urology, The Linyi People’s Hospital, Linyi, China;;National Key Laboratory of Medical Immunology &

关键词: neoleukin-2/15;    OX40 ligand;    cytotoxic activity;    NK cell expansion;    immunotherapy;   

DOI  :  10.3389/fonc.2021.632540

来源: DOAJ

【 摘 要 】

Adoptive natural killer (NK) cell transfer has been demonstrated to be a promising immunotherapy approach against malignancies, but requires the administration of sufficient activated cells for treatment effectiveness. However, the paucity of clinical-grade to support the for large-scale cell expansion limits its feasibility. Here we developed a feeder-based NK cell expansion approach that utilizes OX40L armed NK-92 cell with secreting neoleukin-2/15 (Neo-2/15), a hyper-stable mimetic with a high affinity to IL-2Rβγ. The novel feeder cells (NK92-Neo2/15-OX40L) induced the expansion of NK cells with a 2180-fold expansion (median; 5 donors; range, 1767 to 2719) after 21 days of co-culture without added cytokines. These cells were highly cytotoxic against Raji cells and against several solid tumors in vivo. Mechanistically, NK92-Neo2/15-OX40L induced OX40 and OX40L expression on expanded NK cells and promoted the OX40-OX40L positive feedback loop, thus boosting NK cell function. Our data provided a novel NK cell expansion mechanism and insights into OX40-OX40L axis regulation of NK cell expansion.

【 授权许可】

Unknown