Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA
antibodies. Among TACAs that mediate cell survival signals are the neolactoseries
antigen Lewis Y (LeY) and the
ganglioside GD2. To induce sustained immunity against both LeY and GD2, we developed a
carbohydrate mimicking
peptide (
CMP) as a surrogate pan-immunogen that mimics both. This
CMP, referred to as P10s, is the N-terminal half of a
peptide vaccine named P10s-PADRE, the C-terminal half of which (PADRE) is a Pan-
T-cell epitope. A Phase I dose-escalation trial of P10s-PADRE plus adjuvant MONTANIDE™ ISA 51 VG was conducted in subjects with metastatic
breast cancer to test 300 and 500 μg/injection in two cohorts of 3 subjects each. Doses of the P10s-PADRE
vaccine were administered to research participants subcutaneously on weeks 1, 2, 3, 7 and 19. Antibody responses to P10s, GD2, and LeY were measured by ELISA. The P10s-PADRE
vaccine induced
antibodies specifically reactive with P10s, LeY and GD2 in all 6 subjects. Serum
antibodies displayed Caspase-3-dependent apoptotic functionality against LeY or GD2 expressing
breast cancer cell lines. Immunization with the P10s-PADRE
vaccine was well-tolerated and induced functional
antibodies, and the data suggest potential clinical benefit.