Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro: a novel vaccine for renal cell carcinoma.
Exosome-based immunotherapy for cancer holds promise, but needs improvements, especially for tumor-derived exosomes. We investigated, whether exosomes derived from IL-12-anchored human renal cancer cells could enhance their immunogenicity and increase induction of specific antitumor response. A mammalian co-expression plasmid of glycolipid-anchored-IL-12 (GPI-IL-12) was constructed by subcloning IL-12A chain gene (P35 subunit) and a fusion gene containing GPI-anchor signal sequence of human placental alkaline phosphatase-1 (hPLAP-1) and IL-12B chain gene (P40 subunit) in pBudCE4.1. Then exosomes were prepared from renal cancer cells modified to express GPI-IL-12. The results showed that exosomes derived from IL-12-anchored renal cancer cells expressed renal cell carcinoma-associated antigen G250 and GPI-IL-12. The incorporation of GPI-IL-12 onto exosomes (exosomes-GPI-IL-12, EXO/IL-12) significantly promotes proliferation of T cells, and subsequently increased the release of IFN-gamma. Notably, stimulation with EXOs/IL-12 could efficiently induce antigen-specific cytotoxic T lymphocytes (CTLs), resulting in more significant cytotoxic effects in vitro. These results suggested that exosomes derived from IL-12-anchored renal cancer cells bore GPI-IL-12 and G250, which have tumor rejection antigen with enhanced immunogenicity and antitumor effects, representing a novel strategy of exosomes-based vaccine for renal cell carcinoma.
Zhang
Yao
Y
Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Yi Xue Yuan Road, Chongqing, P.R. China.
Luo
Chun-Li
CL
He
Bai-Cheng
BC
Zhang
Jia-Mo
JM
Cheng
Gang
G
Wu
Xiao-Hou
XH
D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D018664:Interleukin-12; D007371:Interferon-gamma