Abstract

The purpose of the project is to use the MCA-102 model system to elucidate the immunologic mechanisms involved in the rejection of E1A- but not E7-expressing tumor cells, genetically define the components of ElA that are required to induce robust cellular immunity, and further characterize the molecular basis by which ElA but not E7 induces a vigorous cellular immune response in two specific aims.
Specific Aim 1 : Elucidate the key immunologic mechanisms involved in the rejection of tumor cells expressing ElA but not E7. Specifically they will determine the interrelationship and function of NK cells, T cells, perforin- and Fas-mediated lysis and the cytokines, IL-12 and IFNg, in the rejection of E1A- but not E7-expressing tumor cells.
Specific Aim 2 : Define the molecular mechanisms by which E1A-p300 binding and ElA- exon 2 expression activate the NK cell response, thereby triggering a robust cellular immune response against E1A-expressing tumor cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA076491-03
Application #
6172911
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Wong, May
Project Start
1998-09-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$238,667
Indirect Cost

  Institution

Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206

  Publications

Radke, Jay R; Siddiqui, Zeba K; Miura, Tanya A et al. (2008) E1A oncogene enhancement of caspase-2-mediated mitochondrial injury sensitizes cells to macrophage nitric oxide-induced apoptosis. J Immunol 180:8272-9
Miura, Tanya A; Cook, James L; Potter, Terence A et al. (2007) The interaction of adenovirus E1A with p300 family members modulates cellular gene expression to reduce tumorigenicity. J Cell Biochem 100:929-40
Cook, James L; Routes, John M (2005) Adenovirus E1A gene-induced tumor cell rejection through cellular sensitization to immune and nonimmune apoptotic injuries. Front Biosci 10:1396-414
Routes, John M; Ryan, Sharon; Morris, Kristin et al. (2005) Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection. J Exp Med 202:1477-82
Routes, John M; Morris, Kristin; Ellison, Misoo C et al. (2005) Macrophages kill human papillomavirus type 16 E6-expressing tumor cells by tumor necrosis factor alpha- and nitric oxide-dependent mechanisms. J Virol 79:116-23
Miura, Tanya A; Li, Han; Morris, Kristin et al. (2004) Expression of an E1A/E7 chimeric protein sensitizes tumor cells to killing by activated macrophages but not NK cells. J Virol 78:4646-54
Cook, James L; Miura, Tanya A; Ikle, David N et al. (2003) E1A oncogene-induced sensitization of human tumor cells to innate immune defenses and chemotherapy-induced apoptosis in vitro and in vivo. Cancer Res 63:3435-43
Miura, Tanya A; Morris, Kristin; Ryan, Sharon et al. (2003) Adenovirus E1A, not human papillomavirus E7, sensitizes tumor cells to lysis by macrophages through nitric oxide- and TNF-alpha-dependent mechanisms despite up-regulation of 70-kDa heat shock protein. J Immunol 170:4119-26
Cook, J L; Routes, J M (2001) Role of the innate immune response in determining the tumorigenicity of neoplastic cells. Dev Biol (Basel) 106:99-107; discussion 107-8, 143-6
Routes, J M; Ryan, J C; Ryan, S et al. (2001) MHC class I molecules on adenovirus E1A-expressing tumor cells inhibit NK cell killing but not NK cell-mediated tumor rejection. Int Immunol 13:1301-7

Showing the most recent 10 out of 13 publications