A short treatment with galactomannan GM-CT-01 corrects the functions of freshly isolated human tumor-infiltrating lymphocytes

Nathalie Demotte, René Bigirimana, Grégoire Wieërs, Vincent Stroobant, Jean Luc Squifflet, Javier Carrasco, Kris Thielemans, Jean François Baurain, Patrick Van Der Smissen, Pierre J. Courtoy, Pierre Van Der Bruggen

Research output: Contribution to journalArticlepeer-review


Purpose: Several galectins are released by tumor cells and macrophages and accumulate in the tumor microenvironment. Galectin-1 and -3 were found to bind to glycosylated receptors at the surface of tumor-infiltrating lymphocytes (TIL), forming glycoprotein-galectin lattices that could reduce the motility and therefore the functionality of surface molecules. In contrast to blood T cells, human TIL show defective IFN-γ secretion upon ex vivo stimulation. We have previously shown that extracellular galectin-3 participates in the impairment of TIL functions. Indeed, disruption of glycoprotein-galectin-3 lattices using anti-galectin-3 antibodies, or N-acetyllactosamine as a competing sugar, boosted cytokine secretion by TIL. Here we have tested a clinical grade galectin antagonist: GM-CT-01, a galactomannan obtained from guar gum reported to be safe in more than 50 patients with cancer. Experimental Design: TIL were isolated from human tumor ascites, treated for 2 to 20 hours with galectin antagonists and tested for function. Results: We found that GM-CT-01 boosts cytotoxicity of CD8+ TIL and their IFN-γ secretion in a dose-dependent manner. Treating TIL obtained from patients with various cancers, during a few hours, resulted in an increased IFN-γ secretion in up to 80% of the samples. Conclusions: These observations pave the way for investigating the potential benefit of this galectin antagonist in patients with cancer, alone or combined with cancer vaccination, in order to correct in vivo impaired functions of TIL.

Original languageEnglish
Pages (from-to)1823-1833
Number of pages11
JournalClinical Cancer Research
Issue number7
Publication statusPublished - 1 Apr 2014
Externally publishedYes


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