Principal Investigator:<\/strong><\/p>\n\n\n\n Yves St-Pierre Co-investigators<\/strong><\/p>\n\n\n\n David Chatenet<\/strong> Galectins are a family of lectin proteins implicated in tumor progression and immune evasion. When produced in excess by cancer cells, galectins can form homodimers and bind glycans on the surface of T cells. This suppresses the local and systemic immune response in patients, helping tumors to escape immune surveillance and limiting the efficacy of immuno-oncology treatments. To date, most efforts to identify anti-galectin therapeutics have focused on drugs that inhibit binding of galectins to cell surface receptors via their carbohydrate recognition domain (CRD). Unfortunately, most of these attempts have failed.<\/p>\n\n\n\n This project aims to develop a novel class of anti-cancer drugs that specifically inhibit the dimerization of galectins as a means to disrupt their protumorigenic activity. This new mechanism of action is an alternative and\/or complementary solution to CRD inhibitors for cancer treatment. As proof of concept, the project has focused on Galectin-7 (Gal-7), a validated target expressed at high levels in aggressive forms of triple-negative breast cancer. Using a rational design approach, the team has developed two classes of inhibitors: \u201cdimer interfering peptides\u201d (DIPs) and camelid nanobodies (Nbs) to selectively target Gal-7 dimerization and consequently, its functional activity in vitro.<\/p>\n\n\n\n The team has identified four distinct DIP hits and improved their pharmacokinetic properties and potency. In parallel, a platform was used to develop Gal-7-specific single domain nanobodies that have been humanized. Twelve Nbs were identified as hits following an initial screening of a non-immune recombinant camelid antibody synthetic library. Like DIPs, these Nbs are highly specific and have the potential to inhibit Gal-7 via at least two mechanisms of actions, including dimer-interference.<\/p>\n\n\n\n Once validated in animal tumor models, the approach could serve as a template to generate inhibitors against a broad range of galectins implicated in the initiation and progression of cancer, including triple-negative breast cancer.<\/p>\n","protected":false},"featured_media":3823,"template":"","project-category":[97],"class_list":["post-2966","project","type-project","status-publish","has-post-thumbnail","hentry","project-category-biological-and-therapeutic"],"acf":[],"_links":{"self":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/project\/2966","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/project"}],"about":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/types\/project"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/media\/3823"}],"wp:attachment":[{"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/media?parent=2966"}],"wp:term":[{"taxonomy":"project-category","embeddable":true,"href":"https:\/\/cqdm.org\/en\/wp-json\/wp\/v2\/project-category?post=2966"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
<\/strong>INRS-Institut A. Frappier<\/p>\n<\/div>\n\n\n\n
INRS-Institut A. Frappier
Nicolas Doucet<\/strong>
INRS-Institut A. Frappier<\/p>\n<\/div>\n<\/div>\n\n\n\n
\n\n\n\nCompleted\u00a0<\/strong><\/strong><\/strong><\/strong><\/strong>Project<\/strong><\/strong><\/strong><\/strong><\/strong> of $264,000 over 2 years<\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/strong><\/h2>\n\n\n\n
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