Human cancers express tumor antigens that can be targeted by cytolytic T lymphocytes (CTL). These antigens consist of a small peptide, derived from endogenous proteins, that is presented at the cancer cell's surface by an HLA class I molecule. Such antigenic peptides, including MAGE-3.A1 and NA17.A2, have been tested in experimental therapeutic vaccines to elicit CTL responses in cancer patients, mainly with metastatic melanoma. Up to now, only rare tumor responses have been observed.~Tumor resistance to CTL killing is the most likely explanation for the poor effectiveness of cancer vaccines. This resistance is probably acquired by the tumor during its development and selected by its repetitive challenge with spontaneous anti-tumoral immune responses. Recently, we have identified a novel mechanism causing anergy of tumor-associated T lymphocytes, and established new approaches to correct this anergy in vitro. Galectin-3, secreted by tumor cells, appears to inhibit CTL function the co-localization of the T cell receptor and the cluster of differentiation 8 coreceptor. Importantly, this functional defect is restored when anergic T cells are incubated with galectin-3 inhibitors such as the disaccharides lactose and N-acetyllactosamine, and the polysaccharide GM-CT-01. GM-CT-01 is a vegetal galactomannan oligomer, currently under clinical investigation in several types of solid malignancies for its capacity to inhibit galectins and to synergize with chemotherapy drugs.~Our observations suggest that treatment of cancer patients with GM-CT-01 could correct TIL anergy and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination.
The purpose of this study is to determine whether the intravenous and/or GM-CT-01 administration can correct Tumor Infiltrating Lymphocytes (TIL) anergy and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination.