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Recombinant adenoviral vectors have adjuvant activity and stimulate T cell responses against tumor cells

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Author: Geutskens, S.B. · Eb, M.M. van der · Plomp, A.C. · Jonges, L.E. · Cramer, S.J. · Ensink, N.G. · Kuppen, P.J.K. · Hoeben, R.C.
Type:article
Date:2000
Source:Gene Therapy, 16, 7, 1410-1416
Identifier: 235660
Keywords: Cancer gene therapy · IL-2 · Recombinant adenovirus · complementary DNA · cytokine · recombinant interleukin 2 · tumor antigen · virus vector · Adenovirus · Animal cell · Animal experiment · Animal model · Antigen recognition · Antineoplastic activity · Cancer inhibition · Colorectal cancer · Controlled study · Delayed hypersensitivity · DNA transfer · Gene expression · Gene therapy · immune response · Immunotherapy · Liver metastasis · Lymphocyte activation · Nonhuman · Rat strain · T lymphocyte · Transgene · Tumor cell · Tumor regression · Virus plaque · Virus recombinant · Virus replication · Adenoviridae · Animals · Colorectal Neoplasms · Flow Cytometry · Gene Therapy · Genetic Vectors · Histocompatibility Antigens Class I · Histocompatibility Antigens Class II · Humans · Intercellular Adhesion Molecule-1 · Interleukin-2 · Liver Neoplasms, Experimental · Lymphocyte Activation · Rats · Rats, Inbred Strains · T-Lymphocytes · Tumor Cells, Cultured · Adenoviridae · Animalia · DNA viruses

Abstract

The host-immune response against adenoviruses forms a major obstacle for their use as gene therapy vectors for treatment of genetic defects. None the less, they are the preferred vectors for in vivo gene transfer in experimental gene therapy protocols for cancer. In this article we demonstrate the antitumor efficacy of adenovirus-mediated transfer of human interleukin-2 cDNA in the rat-CC531 model for hepatic metastases of colorectal cancer: intratumoral administration of 108 plaque-forming units of the hIL-2-expressing adenoviral vector, AdCAIL-2, resulted in a cessation of tumor growth in 80% of the injected tumors. In control groups receiving AdCnull, a vector with the same viral backbone, but lacking transgene expression, none of the tumors responded. However, intratumoral treatment with this vector significantly enhanced tumor regression induced by systemic IL-2 protein treatment, which was used as a positive control. In addition we show, by performing delayed-type of hypersensitivity assays, that AdCnull when injected intratumorally enhances recognition of tumor antigens by T lymphocytes to the same extent as intratumoral treatment with the IL-2-expressing vector. The replication-deficient adenoviruses appear to have a therapeutic advantage in cytokinemediated immunotherapy: even adenovirus vectors that do not express a transgene, show adjuvant activity and stimulate an antitumor immune response. Chemicals/CAS: Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Intercellular Adhesion Molecule-1, 126547-89-5; Interleukin-2