Immunization of Metastatic Breast Cancer Patients with CD80-Modified Breast Cancer Cells and GM-CSF

Tumor-associated antigens have been identified on a variety of human neoplasms. Each of these antigens may be able to serve as a target for an immune response, the result of which would be elimination of the tumor cell. An essential component of this immune response is the presentation of antigen to potential effector cells. This can be accomplished via host professional antigen-presenting cells (APC), such as dendritic cells, or via the tumor itself. The lack of information about tumor-associated antigens and their apparent lack of immunogenicity in vivo complicate the induction of immune responses against breast cancers. We have undertaken the effort to increase the antigen-presenting cell (APC) function of a breast cancer line that expresses at least one tumor-associated antigen, Her2/neu. The her2/neu gene encodes a 185-kd transmembrane tyrosine kinase receptor that shares homology with the epidermal growth factor receptor. Previous studies indicated that Her2/neu was overexpressed by 20–30% of breast and ovarian tumors and its overexpression has been associated with a poor prognosis [1, 2], Studies have also suggested that Her2/neu can also function as a tumor-associated antigen. Cytotoxic T lymphocytes (CTL) isolated from ovarian tumors specifically recognizes Her2/neu-derived peptides and can kill Her2/neu+ tumors but not Her2/neu- tumors [3, 4]. Antibodies to Her2/neu can be found in the sera of patients with metastatic breast cancer but not in control subjects [5,6]. In addition, rats immunized with Her2/neu peptides developed CD4+ T cell immune responses as well as antibody responses [7] and mice immunized with Her2/neu peptides developed Her2/neu-specific tumor immunity [8].