The overall objective of this work is to produce and characterize monoclonal antibodies directed to nonsmall cell lung carcinoma and then use these monoclonal antibodies to treat lung carcinomas established in athymic mice. During the past 12 months, we have thoroughly characterized an existing panel of monoclonal antibodies and selected two, KS1/4 and KS1/9, for further studies. Additionally, we have produced more monoclonal antibodies directed to lung squamous carcinoma and a metastasized adenocarcinoma. In the next year, we plan to: (1) test MoAb KS1/4 and KS1/9 as to their ability to kill established tumors in athymic mice; (2) biochemically characterize the antigens with which KS1/4 and KS1/9 are reactive. This will involve HPLC isolation, limited amino acid sequence analysis, and TLC antibody overlay to identify the KS1/9 antigen; (3) assess the density of KS1/4 and KS1/9 antigens on a panel of tumor cells by FACS analysis; (4) continue testing MoAb KS1/4 and KS1/9 in immunotherapeutic agents for lung tumors established in athymic mice; and (5) characterize the new monoclonal antibodies to squamous carcinoma by immunoperoxidase staining of fresh frozen and paraffin-embedded normal and tumor tissues. (AB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034778-03
Application #
3172578
Study Section
Experimental Immunology Study Section (EI)
Project Start
1983-05-01
Project End
1986-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037
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Elias, D J; Hirschowitz, L; Kline, L E et al. (1990) Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma. Cancer Res 50:4154-9
Perez, M S; Walker, L E (1989) Isolation and characterization of a cDNA encoding the KS1/4 epithelial carcinoma marker. J Immunol 142:3662-7
Shani, J; Mohd, S; Wolf, W et al. (1989) Compartmental biodistribution of a monoclonal antibody against human lung adenocarcinoma grown in athymic mice. Int J Rad Appl Instrum B 16:33-40
Fernsten, P D; Pekny, K W; Harper, J R et al. (1987) Antigenic mimicry of a human cellular polypeptide by Mycoplasma hyorhinis. Infect Immun 55:1680-5
Fernsten, P D; Pekny, K W; Reisfeld, R A et al. (1986) Antigens associated with human squamous cell lung carcinoma defined by murine monoclonal antibodies. Cancer Res 46:2970-7
Shani, J; Wolf, W; Chanachai, W et al. (1986) Labeling and comparative biodistribution of the monoclonal antibody KS1/4 in nude mice bearing human lung adenocarcinoma. Int J Rad Appl Instrum B 13:379-82