Abstract

The overall objective of the proposed research is to dissect the role of SV40 tumor or T antigen in the expression of SV40 transplantation rejection antigen (TrAg) at surface SV40 infected or transformed cells. We have demonstrated that the TrAg antigenic sites exist on T antigen, however, the distribution of these sites on T antigen remains unknown. We now propose to determine (1) the segments of SV40 early region which are involved in TrAg expression, (2) the localization of SV40 early gene products at the surface of SV40 infected and transformed cells, (3) whether T antigen at the cell surface directly acts as a target for cytotoxic lymphocytes, (4) domains of T antigen which possess TrAg activity, and (5) to compare TrAg specified by SV40 and the related human papovavirus BK in mouse cells transformed by these viruses. The approaches described above will allow us to seek evidence for the direct relationship between SV40 T antigen and TrAg recognized by the cytotoxic lymphocytes by using genetic, immunological and recombinant DNA approaches.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025000-10
Application #
3166629
Study Section
Virology Study Section (VR)
Project Start
1978-06-01
Project End
1988-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
10
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033

  Publications

Ward-Kavanagh, Lindsay K; Kokolus, Kathleen M; Cooper, Timothy K et al. (2018) Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors. Cancer Immunol Immunother 67:639-652
Li, Guangfu; Liu, Dai; Cooper, Timothy K et al. (2017) Successful chemoimmunotherapy against hepatocellular cancer in a novel murine model. J Hepatol 66:75-85
Memarnejadian, Arash; Meilleur, Courtney E; Shaler, Christopher R et al. (2017) PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8+ T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination. J Immunol 199:3348-3359
Cozza, Eugene M; Cooper, Timothy K; Budgeon, Lynn R et al. (2015) Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors. Cancer Immunol Immunother 64:325-36
Ward-Kavanagh, Lindsay K; Zhu, Junjia; Cooper, Timothy K et al. (2014) Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer. Cancer Immunol Res 2:777-88
Rytelewski, Mateusz; Meilleur, Courtney E; Yekta, Maryam Atef et al. (2014) Suppression of immunodominant antitumor and antiviral CD8+ T cell responses by indoleamine 2,3-dioxygenase. PLoS One 9:e90439
Goodwin, Erin M; Zhong, Qing; Abendroth, Catherine S et al. (2013) Anaplastic renal carcinoma expressing SV40 T antigen in a female TRAMP mouse. Comp Med 63:338-41
Wilson, Jarad J; Pack, Christopher D; Lin, Eugene et al. (2012) CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. J Immunol 188:4340-8
Watson, Alan M; Mylin, Lawrence M; Thompson, Megan M et al. (2012) Modification of a tumor antigen determinant to improve peptide/MHC stability is associated with increased immunogenicity and cross-priming a larger fraction of CD8+ T cells. J Immunol 189:5549-60
Maleki Vareki, S; Harding, M J; Waithman, J et al. (2012) Differential regulation of simultaneous antitumor and alloreactive CD8(+) T-cell responses in the same host by rapamycin. Am J Transplant 12:233-9

Showing the most recent 10 out of 63 publications