ArticleGene therapy1999
Co-delivery of T helper 1-biasing cytokine genes enhances the efficacy of gene gun immunization of mice: studies with the model tumor antigen beta-galactosidase and the BALB/c Meth A p53 tumor-specific antigen.
Article in Gene therapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 46 citations in OpenAlex.
- Identification of a 17beta-hydroxysteroid dehydrogenase type 12 pseudogene as the source of a highly restricted BALB/c Meth A tumor rejection peptide.Cancer immunology, immunotherapy : CII · 2010Article
- Development of multi-epitope vaccines targeting wild-type sequence p53 peptides.Expert review of vaccines · 2008Review
- Article
- Vaccination with liposome--DNA complexes elicits enhanced antitumor immunity.Cancer gene therapy · 2006Article
- Low dose and gene gun immunization with a hepatitis C virus nonstructural (NS) 3 DNA-based vaccine containing NS4A inhibit NS3/4A-expressing tumors in vivo.Gene therapy · 2003Article
- Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy.Gene therapy · 2002Article
- Immunogenicity of enhanced green fluorescent protein (EGFP) in BALB/c mice: identification of an H2-Kd-restricted CTL epitope.Gene therapy · 2000Article
- Gene therapy for carcinoma of the breast: Genetic immunotherapy.Breast cancer research : BCR · 2000Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
DNA-based immunization is currently being investigated as a new method for the induction of cellular and humoral immunity directed against viral disease and cancer. In the present study we characterized and compared the immune responses induced in mice following particle-bombardment of the skin ('gene gun' immunization) with those elicited by intracutaneous injection of a recombinant adenoviral vector. Using the well characterized beta-galactosidase (beta gal) model Ag system we find that both in vivo gene transfer systems elicit potent and long-lasting anti-beta gal-specific CD8+ and CD4+ T cell responses. However, gene gun immunization predominantly promotes the production of anti-beta gal antibodies of the gamma 1 isotype, indicative of a Th2-biased immune response, while intradermal injection of recombinant adenovirus primarily leads to the production of anti-beta gal gamma 2a antibodies, indicative of a Th1-biased immune response. Since viral infections are generally associated with the production of large amounts of IFN-alpha and IL-12, we investigated whether administration of expression plasmids encoding these Th1-associated cytokines along with antigen-encoding cDNA can influence the nature of the immune response resulting from gene gun immunization. We observed that co-delivery of IFN-alpha or IL-12 resulted in increased production of anti-beta gal gamma 2a antibodies. This suggests a shift towards a Th1 phenotype of the resulting immune response, thus mimicking a viral infection. Importantly, gene gun immunization of mice with a naturally occurring tumor antigen, the tumor-specific p53 mutant antigen expressed by the chemically induced BALB/c Meth A sarcoma, required co-delivery of IL-12 for the induction of effective antitumor immunity. These results have important implications for the design of clinically relevant gene gun immunization strategies for tumor immunotherapy.
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