Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice

Yoshio Sakai, Brian J. Morrison, J. Douglas Burke, Jong Myun Park, Masaki Terabe, John Edward Janik, Guido Forni, Jay A. Berzofsky, John C. Morris

Research output: Contribution to journalArticle

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Abstract

Dendritic cells (DCs) are powerful antigen-presenting cells that process antigens and present peptide epitopes in the context of the major histocompatibility complex molecules to generate immune responses. DCs are being studied as potential anticancer vaccines because of their ability to present antigens to naïve T cells and to stimulate the expansion of antigen-specific T-cell populations. We investigated an antitumor vaccination using DCs modified by transfer of a nonsignaling neu oncogene, a homologue of human HER-2/neu, in a transgenic model of breast cancer. BALB-neuT mice develop breast cancers as a consequence of mammary gland-specific expression of an activated neu oncogene. We vaccinated BALB-neuT mice with bone marrow-derived DCs transduced with Ad.Neu, a recombinant adenovirus expressing a truncated neu oncoprotein. The vaccine stimulated the production of specific anti-neu antibodies, enhanced interferon-γ expression by T cells, and prevented or delayed the onset of mammary carcinomas in the mice. Over 65% of vaccinated mice remained tumor free at 28 weeks of age, whereas all of the mice in the control groups developed tumors. When challenged with a neu-expressing breast cancer cell line, vaccinated tumor-free animals had delayed tumor growth compared with controls. The antitumor effect of the vaccine was specific for expression of neu. Studies showed that CD4+ T cells were required in order to generate antitumor immunity. Importantly, the effectiveness of the vaccine was not diminished by preexisting immunity to adenovirus, whereas the protection afforded by vaccination that used direct injection of Ad.Neu was markedly reduced in mice with antiadenovirus antibody titers. DCs modified by recombinant adenoviruses expressing tumor-associated antigens may provide an effective antitumor vaccination strategy.

Original languageEnglish (US)
Pages (from-to)8022-8028
Number of pages7
JournalCancer Research
Volume64
Issue number21
DOIs
StatePublished - Nov 1 2004

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Oncogenes
Dendritic Cells
Transgenic Mice
Vaccination
Breast Neoplasms
Vaccines
Adenoviridae
T-Lymphocytes
Antigens
Immunity
Neoplasms
Oncogene Proteins
Neoplasm Antigens
Antigen-Presenting Cells
Human Mammary Glands
Tumor Cell Line
Major Histocompatibility Complex
Interferons
Epitopes
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. / Sakai, Yoshio; Morrison, Brian J.; Burke, J. Douglas; Park, Jong Myun; Terabe, Masaki; Janik, John Edward; Forni, Guido; Berzofsky, Jay A.; Morris, John C.

In: Cancer Research, Vol. 64, No. 21, 01.11.2004, p. 8022-8028.

Research output: Contribution to journalArticle

Sakai, Y, Morrison, BJ, Burke, JD, Park, JM, Terabe, M, Janik, JE, Forni, G, Berzofsky, JA & Morris, JC 2004, 'Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice', Cancer Research, vol. 64, no. 21, pp. 8022-8028. https://doi.org/10.1158/0008-5472.CAN-03-3442
Sakai, Yoshio ; Morrison, Brian J. ; Burke, J. Douglas ; Park, Jong Myun ; Terabe, Masaki ; Janik, John Edward ; Forni, Guido ; Berzofsky, Jay A. ; Morris, John C. / Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. In: Cancer Research. 2004 ; Vol. 64, No. 21. pp. 8022-8028.
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AU - Terabe, Masaki

AU - Janik, John Edward

AU - Forni, Guido

AU - Berzofsky, Jay A.

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