Exosomes Derived From IL-12-anchored Renal Cancer Cells Increase Induction of Specific Antitumor Response in Vitro: A Novel Vaccine for Renal Cell Carcinoma

Int J Oncol. 2010 Jan;36(1):133-40.

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.

MeSH terms

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

Substances

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