Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro: a novel vaccine for renal cell carcinoma.

Abstract

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.

• Authors: Yao Zhang, Chun-Li Luo, Bai-Cheng He, Jia-Mo Zhang, Gang Cheng, Xiao-Hou Wu
• Journal: International journal of oncology (Int J Oncol) Vol. 36 Issue 1 Pg. 133-40 (Jan 2010) ISSN: 1791-2423 [Electronic] Greece
• PMID: 19956842 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• Cancer Vaccines
• Interleukin-12
• Interferon-gamma

Topics

• Antigens, Neoplasm (metabolism)
• Antineoplastic Agents (pharmacology)
• Cancer Vaccines (therapeutic use)
• Carcinoma, Renal Cell (metabolism, therapy)
• Cell Line, Tumor
• Cell Proliferation
• Exosomes (metabolism)
• Humans
• Interferon-gamma (metabolism)
• Interleukin-12 (metabolism)
• Kidney Neoplasms (metabolism, therapy)
• Leukocytes, Mononuclear (cytology)
• Microscopy, Confocal (methods)
• Microscopy, Electron, Transmission (methods)
• T-Lymphocytes, Cytotoxic (metabolism)