Vaccine Treatment for Advanced Breast Cancer

According to 2002 statistics of the American Cancer Society, an estimated 203,500 individuals will be diagnosed with breast cancer and 39,600 will die of the disease this year despite all current therapy. This protocol attempts to exploit an approach to breast cancer gene therapy using a naturally occurring barrier to xenotransplantation in humans in attempt to vaccinate patients against their breast cancer. The expression of the murine alpha (1,3) galactosyltransferase \[alpha (1,3) GT\] gene results in the cell surface expression of alpha (1,3) galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation. These antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with relapsed or refractory breast cancer will undergo a series of four intradermal injections with a vaccine composed of irradiated allogeneic breast cancer cell lines (HAB-1 and HAB-2) that have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine alpha (1,3) GT gene. Endpoints of the study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and immunological responses.