The hypothesis to be tested in this project is that there are tumor specific antigenic determinants recognized, in association with MHC, by autologous tumor-specific T-cell clones. The overall objective is to identify these tumor-specific antigenic determinants.
The specific aims are: 1) to clone and determine the sequence of the """"""""tumor-specific antigen"""""""" involved: a) to construct on a retroviral vector a cDNA library from an appropriate melanoma tumor cell clone expressing """"""""tumor-specific antigen""""""""; b) to infect autologous recipient cells (EBV B-cell lines or melanoma clones not expressing the """"""""tumor-specific antigen"""""""") with the retrovirus; c) to identify recipient cells expressing """"""""tumor-specific antigen"""""""" by their ability to stimulate autologous tumor-specific TIL T-cell clones. To confirm the expression of """"""""tumor-specific antigen"""""""" by the recipient cells by their susceptibility to lysis by autologous tumor-specific TIL T cell clones; to clone the gene encoding for the """"""""tumor-specific antigen"""""""" from the recipient cells and determine its sequence; e) to employ the cosmid library/P815.P1.HTR transfection procedure of Boon et al as an alternative approach, in the event that the retroviral cDNA library does not permit the expression of """"""""tumor-specific antigen"""""""" on recipient cells. 2) To identify the peptide of the """"""""tumor-specific antigen"""""""" that is recognized in association with self-MHC by autologous tumor-specific T cells. These studies are hoped to improve on understanding of the response of the immune system to tumor cells, the immunogenicity of tumors, and the mechanism(s) of immune surveillance and tumor containment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA052308-01A1
Application #
3197100
Study Section
Experimental Immunology Study Section (EI)
Project Start
1991-07-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Platsoucas, Chris D; Fincke, John E; Pappas, John et al. (2003) Immune responses to human tumors: development of tumor vaccines. Anticancer Res 23:1969-96
Kooi, S; Zhang, H Z; Patenia, R et al. (1996) HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2. Cell Immunol 174:116-28
Freedman, R S; Platsoucas, C D (1996) Immunotherapy for peritoneal ovarian carcinoma metastasis using ex vivo expanded tumor infiltrating lymphocytes. Cancer Treat Res 82:115-46
Nash, M A; Platsoucas, C D; Wong, B Y et al. (1995) Transduction of rIL-2 expanded CD4+ and CD8+ ovarian TIL-derived T cell lines with the G1Na (neor) replication-deficient retroviral vector. Hum Gene Ther 6:1379-89
Freedman, R S; Tomasovic, B; Templin, S et al. (1994) Large-scale expansion in interleukin-2 of tumor-infiltrating lymphocytes from patients with ovarian carcinoma for adoptive immunotherapy. J Immunol Methods 167:145-60
Lee, J E; Reveille, J D; Ross, M I et al. (1994) HLA-DQB1*0301 association with increased cutaneous melanoma risk. Int J Cancer 59:510-3
Chen, P F; Freedman, R S; Chernajovsky, Y et al. (1994) Amplification of immunoglobulin transcripts by the non-palindromic adaptor polymerase chain reaction (NPA-PCR). Nucleotide sequence analysis of two human monoclonal antibodies recognizing two cell surface antigens expressed in ovarian, cervix, breast, col Hum Antibodies Hybridomas 5:131-42
Mitropoulos, D; Kooi, S; Rodriguez-Villanueva, J et al. (1994) Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma. Clin Exp Immunol 97:321-7
Mathioudakis, G; Chen, P F; Li, Y D et al. (1993) Preferential rearrangements of the V gamma I subgroup of the gamma-chain of the T-cell antigen receptor to J gamma 2C gamma 2 gene segments in peripheral blood lymphocyte transcripts from normal donors. Scand J Immunol 38:31-6
Kooi, S; Freedman, R S; Rodriguez-Villanueva, J et al. (1993) Cytokine production by T-cell lines derived from tumor-infiltrating lymphocytes from patients with ovarian carcinoma: tumor-specific immune responses and inhibition of antigen-independent cytokine production by ovarian tumor cells. Lymphokine Cytokine Res 12:429-37

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