We intend to use genetic engineering to generate mouse tumor cell lines that express at the cell surface p97, a human melanoma-associated antigen, and to produce large amounts of p97. This will provide a unique model system in which to evaluate the effectiveness of immunization with a human tumor-associated antigen in inducing tumor reJection. A nonhuman primate model will be used to determine whether immunization with p97 is effective when the antigen is present in small amounts in normal tissues. We have three specific aims: (1) cloning p97 mRNA and gene. We intend (a) to clone and sequence p97 mRNA and (b) to clone the p97 gene; (2) expression of p97. We intend (a) to generate mouse tumor cell lines that express p97 at the cell surface and (b) to produce large amounts of p97 and antigenic fragments of p97; (3) evaluation of p97 as a melanoma vaccine. We intend to determine (a) whether immunization of mice with p97 leads to rejection of mouse tumors expressing p97 and (b) whether non-human primates can be immunized against p97. There has been no request for support for subsequent studies with human subjects, which will be undertaken if the preclinical studies are successful. (TA)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038415-03
Application #
3176547
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-03-15
Project End
1987-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Oncogen
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98121
Liao, S K; Khosravi, M J; Brown, J P et al. (1987) Difference in cell binding patterns of two monoclonal antibodies recognizing distinct epitopes on a human melanoma-associated oncofetal antigen. Mol Immunol 24:1-9
Rose, T M; Plowman, G D; Teplow, D B et al. (1986) Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence. Proc Natl Acad Sci U S A 83:1261-5
Le Beau, M M; Diaz, M O; Plowman, G D et al. (1986) Chromosomal sublocalization of the human p97 melanoma antigen. Hum Genet 72:294-6