Skip to main content
Journal cover image

Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.

Publication ,  Journal Article
Osada, T; Berglund, P; Morse, MA; Hubby, B; Lewis, W; Niedzwiecki, D; Yang, XY; Hobeika, A; Burnett, B; Devi, GR; Clay, TM; Smith, J; Kim Lyerly, H
Published in: Cancer Immunol Immunother
November 2012

We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

November 2012

Volume

61

Issue

11

Start / End Page

1941 / 1951

Location

Germany

Related Subject Headings

  • Virion
  • T-Lymphocytes
  • Replicon
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Interleukin-12
  • Immunology
  • Humans
  • Encephalitis Virus, Venezuelan Equine
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Osada, T., Berglund, P., Morse, M. A., Hubby, B., Lewis, W., Niedzwiecki, D., … Kim Lyerly, H. (2012). Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects. Cancer Immunol Immunother, 61(11), 1941–1951. https://doi.org/10.1007/s00262-012-1248-y
Osada, Takuya, Peter Berglund, Michael A. Morse, Bolyn Hubby, Whitney Lewis, Donna Niedzwiecki, Xiao Yi Yang, et al. “Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.Cancer Immunol Immunother 61, no. 11 (November 2012): 1941–51. https://doi.org/10.1007/s00262-012-1248-y.
Osada T, Berglund P, Morse MA, Hubby B, Lewis W, Niedzwiecki D, et al. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects. Cancer Immunol Immunother. 2012 Nov;61(11):1941–51.
Osada, Takuya, et al. “Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.Cancer Immunol Immunother, vol. 61, no. 11, Nov. 2012, pp. 1941–51. Pubmed, doi:10.1007/s00262-012-1248-y.
Osada T, Berglund P, Morse MA, Hubby B, Lewis W, Niedzwiecki D, Yang XY, Hobeika A, Burnett B, Devi GR, Clay TM, Smith J, Kim Lyerly H. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects. Cancer Immunol Immunother. 2012 Nov;61(11):1941–1951.
Journal cover image

Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

November 2012

Volume

61

Issue

11

Start / End Page

1941 / 1951

Location

Germany

Related Subject Headings

  • Virion
  • T-Lymphocytes
  • Replicon
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Interleukin-12
  • Immunology
  • Humans
  • Encephalitis Virus, Venezuelan Equine