One in six people will die of cancer. the systemic nature, recall ability and exquisite specificity of the immune system makes immunotherapy an attractive prospect for cancer treatment. Hepatocellular carcinoma, cervical carcinoma, various leukemias and lymphomas all have proposed viral etiologies. Viral encoded tumor specific antigens make viral associated tumors strong candidates for immunotherapy. Recent studies have described the presence of simian virus 40 (SV40)-like gene sequences and proteins (specifically the large tumor antigen: SV40 Tag) in human osteosarcomas, glioblastomas, ependymomas and malignant pleural mesotheliomas (MPM), demonstrating SV40 association with certain human malignancies. To facilitate the development of human clinical protocols for the immunotherapy of SV40 associated human malignancies, the proposed study will employ an SV40 murine tumor system to evaluate the efficacy of CTL transfer therapies and peptide based vaccines designed to target an immune response to SV40 Tag expressing tumors in vivo. Briefly, SV40 Tag specific CTL will be generated by immunization of Balb/c mice with SV40 Tag gene constructs and the epitope specificity determined by using selected H-2d restricted synthetic peptides representing potential CTL epitopes on SV40 Tag. These CTL will be utilized to examine the ability of adoptively transferred T cells to protect against tumor challenge in syngeneic mice. Further, selected synthetic peptides will be examined for the ability to actively induce protective tumor immunity in vivo. Completion of this study will provide valuable information on the active induction of tumor destructive immunity involving SV40 Tag-epitope specific CTL in vivo. Moreover, the information generated using the murine SV40 tumor model will expedite the development of reagents and clinical trials designed to examine SV40 Tag specific immunotherapies for SV40 associated human malignancies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
7R29CA077351-03
Application #
6085902
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Program Officer
Hecht, Toby T
Project Start
1998-04-01
Project End
2003-03-31
Budget Start
1999-07-01
Budget End
2000-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Providence Portland Medical Center
Department
Type
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97213
Payton, Laura A; Lewis, Jennifer D; Byrne, Jennifer A et al. (2008) Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity. Cancer Immunol Immunother 57:799-811
Lewis, Jennifer D; Payton, Laura A; Whitford, Jill G et al. (2007) Induction of tumorigenesis and metastasis by the murine orthologue of tumor protein D52. Mol Cancer Res 5:133-44
Lowe, Devin B; Shearer, Michael H; Tarbox, James A et al. (2005) In vitro simian virus 40 large tumor antigen expression correlates with differential immune responses following DNA immunization. Virology 332:28-37
Lewis, Jennifer D; Shearer, Michael H; Kennedy, Ronald C et al. (2005) Surrogate tumor antigen vaccination induces tumor-specific immunity and the rejection of spontaneous metastases. Cancer Res 65:2938-46
Kennedy, Ronald C; Shearer, Michael H; Lowe, Devin B et al. (2004) Anti-idiotype responses abrogate anti-CD4-induced tolerance to a tumor-specific antigen and promote systemic tumor immunity. Cancer Immunol Immunother 53:987-94
Lewis, Jennifer D; Reilly, Brian D; Bright, Robert K (2003) Tumor-associated antigens: from discovery to immunity. Int Rev Immunol 22:81-112
Kennedy, Ronald C; Shearer, Michael H; Watts, Allison M et al. (2003) CD4+ T lymphocytes play a critical role in antibody production and tumor immunity against simian virus 40 large tumor antigen. Cancer Res 63:1040-5
Watts, A M; Bright, R K; Kennedy, R C (2000) DNA cancer vaccination strategies target SV40 large tumour antigen in a murine experimental metastasis model. Dev Biol (Basel) 104:143-7
Watts, A M; Shearer, M H; Pass, H I et al. (1999) Comparison of simian virus 40 large T antigen recombinant protein and DNA immunization in the induction of protective immunity from experimental pulmonary metastasis. Cancer Immunol Immunother 47:343-51