Characterization of Membrane Antigens of Human Squamous Cell Carcinoma Using Monoclonal Antibodies.

Abstract

Tumor-specific cell-surface antigens have been clearly demonstrated on experimentally induced animal tumors and evidence also exists that human tumors may express antigens not found on normal cells. To determine whether tumor-specific antigens could be detected on human squamous cell carcinoma (SCC), murine monoclonal antibodies were raised to cultured SCC cells and tested for reactivity to cultured tumor cells and normal cells of many histologic types. No tumor-specific reagents were obtained, but several antibodies proved to have useful applications to the study of cancer biology. Antibody E7 defines a human species-specific antigen which maps to a locus on the short arm of chromosome 11. This region is deleted from one chromosome in patients with Wilm's tumor, a rare form of cancer. Antibody G6 defines an antigen present on fifty percent or normal cells and most tumor types, but is present on over ninety percent of squamous carcinomas. The expression of this antigen may be related to malignant transformation of SCC and some related tumors. Antibody G10 detects the type 2 H blood group antigen, a tissue-specific antigen expressed on malignant as well as normal squamous cells. Antibody A9 detects a differentiation antigen present on most SCC as well as normal basal and parabasal cells. This antigen was not identified but appears to be a secreted product associated with the basement membrane region of normal epidermis. The failure to detect a SCC-specific tumor antigen may be due to the inability of the murine immune system to recognize a human tumor-specific antigen. It may also reflect a situation in which such a small number of cells were sensitized to a given antigen that the probability of selecting the appropriate antibody-producing clone was extremely small. However, these studies have demonstrated that useful reagents can be produced in mice to human cells even if none detect a tumor-specific antigen. In addition to diagnostic applications, these monoclonal antibodies can be used to study gene expression in malignant cells to (1) compare antigenic and genetic characteristics of cancer cells with their normal counterparts and (2) determine developmental relationships between SCC and tumors of other histologic types.