A Phase I/II Study of an Antitumor Vaccination Using Alpha(1,3)Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Refractory or Recurrent Malignant Melanoma
According to statistics of the American Cancer Society, an estimated 55,000 individuals will
be diagnosed with malignant melanoma and 8,000 will die of the disease this year in the
Unites States despite all current therapy. This protocol attempts to exploit an approach to
melanoma vaccine therapy using a naturally occurring barrier to xenotransplantation in
humans in attempt to vaccinate patients against their melanoma 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
advanced stage melanoma will undergo a series of twelve intradermal injections with a
trivalent vaccine composed of irradiated allogeneic melanoma cell lines (HAM-1, HAM-2 and
HAM-3). These cell lines 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the side effects, dose-limiting toxicity and maximum tolerated dose.
Ronald C. DeConti, M.D.
University of South Florida
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center & Research Institute||Tampa, Florida 33612|