Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model

• Published in: Cancer letters Vol. 299; no. 2; pp. 95 - 110
• Main Authors: Stannard, Kimberley A, Collins, Patrick M, Ito, Koichi, Sullivan, Emily M, Scott, Stacy A, Gabutero, Elwyn, Darren Grice, I, Low, Pauline, Nilsson, Ulf. J, Leffler, Hakon, Blanchard, Helen, Ralph, Stephen J
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.12.2010; Elsevier Limited
• Subjects: Animals; Antigens; Apoptosis; Binding sites; Blotting, Western; Breast cancer; Cancer and Oncology; Cancer och onkologi; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Carbohydrates; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cell Proliferation - drug effects; Clinical Medicine; Clinical trials; Crystallography, X-Ray; Cytokines; Cytotoxicity, Immunologic - drug effects; Disaccharides; Disaccharides - chemistry; Disaccharides - metabolism; Disaccharides - pharmacology; Female; Galectin 1 - chemistry; Galectin 1 - genetics; Galectin 1 - metabolism; Galectin 3 - chemistry; Galectin 3 - genetics; Galectin 3 - metabolism; Galectin-1 inhibitor; Galectins - chemistry; Galectins - genetics; Galectins - metabolism; Hematology, Oncology and Palliative Medicine; Humans; Immunity - drug effects; Immunotherapy - methods; Klinisk medicin; Ligands; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - therapy; Medical and Health Sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred Strains; Models, Molecular; Protein Binding; Studies; T cell receptors; T-cells; Thiogalactosides - chemistry; Thiogalactosides - metabolism; Thiogalactosides - pharmacology; Tumor Burden - drug effects; Tumors; Tumour immunity; T-cells; Galectin-1 inhibitor; thiodigalactoside; rhGal-1; Disaccharides; TDG; Tumour immunity; recombinant human galectin-1 protein; LBA; lactose; lactobionic acid; LAC
• ISSN: 0304-3835; 1872-7980; 1872-7980
• DOI: 10.1016/j.canlet.2010.08.005

Abstract High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV - c - neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8+ CTL’s killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo.