Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity

Mary L. Disis, Nathalie Scholler, Amber Dahlin, Janice Pullman, Keith L Knutson, Karl Erik Hellstrom̈, Ingegerd Hellstrom̈

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

DNA vaccines are ideally suited for immunizing against tumor antigens because constructs can be formulated that not only encode the tumor antigen but also encode molecules chosen to improve the ability to elicit an antitumor response. Ligands expressed on antigen-presenting cells associated with stimulating a robust T-cell response are excellent candidates for inclusion in a DNA vaccine. Mice transgenic for the HER-2/neu homologue, rat neu, were immunized with full-length rat neu cDNA given alone or in combination with plasmids encoding costimulatory molecules CD80 or CD86 and the ligand for CD137 (CD137L). Intradermal injection of the plasmid constructs resulted in both plasmid transcript and antigen protein expression being detected in lymph nodes draining the injection site. Immunization with plasmids encoding the neu antigen along with plasmids encoding CD137L and either CD80 or CD86 resulted in the generation of neu-specific antibodies that induced phopshorylation of the neu tyrosine kinase and inhibited the growth of cultured tumor cells overexpressing neu. Survival of animals was significantly prolonged after immunization with vaccines encoding neu together with the costimulatory molecules. Although tumors eventually occurred in the vaccinated animals, they were markedly infiltrated with CD4+ T cells. DNA vaccines encoding neu, when given in combination with both CD137L and either CD80 or CD86, can induce cellular and humoral immunity and result in an antitumor effect.

Original languageEnglish (US)
Pages (from-to)995-1002
Number of pages8
JournalMolecular Cancer Therapeutics
Volume2
Issue number10
StatePublished - Oct 2003
Externally publishedYes

Fingerprint

Immunity
Plasmids
Vaccines
DNA Vaccines
Neoplasm Antigens
Immunization
4-1BB Ligand
Cultured Tumor Cells
T-Lymphocytes
Antigens
Intradermal Injections
Antigen-Presenting Cells
Humoral Immunity
Cellular Immunity
Protein-Tyrosine Kinases
Transgenic Mice
Complementary DNA
Lymph Nodes
Ligands
Injections

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Drug Discovery
  • Pharmacology

Cite this

Disis, M. L., Scholler, N., Dahlin, A., Pullman, J., Knutson, K. L., Hellstrom̈, K. E., & Hellstrom̈, I. (2003). Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity. Molecular Cancer Therapeutics, 2(10), 995-1002.

Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity. / Disis, Mary L.; Scholler, Nathalie; Dahlin, Amber; Pullman, Janice; Knutson, Keith L; Hellstrom̈, Karl Erik; Hellstrom̈, Ingegerd.

In: Molecular Cancer Therapeutics, Vol. 2, No. 10, 10.2003, p. 995-1002.

Research output: Contribution to journalArticle

Disis, ML, Scholler, N, Dahlin, A, Pullman, J, Knutson, KL, Hellstrom̈, KE & Hellstrom̈, I 2003, 'Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity', Molecular Cancer Therapeutics, vol. 2, no. 10, pp. 995-1002.
Disis, Mary L. ; Scholler, Nathalie ; Dahlin, Amber ; Pullman, Janice ; Knutson, Keith L ; Hellstrom̈, Karl Erik ; Hellstrom̈, Ingegerd. / Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity. In: Molecular Cancer Therapeutics. 2003 ; Vol. 2, No. 10. pp. 995-1002.
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