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Casting off with CD206
CAMBRIDGE, Mass.—BIND Therapeutics Inc. and Dublin, Ohio-based Macrophage Therapeutics, a subsidiary of Navidea Biopharmaceuticals Inc., have launched a research collaboration to engineer Accurins using the Manocept targeting platform, which allows for selective, efficient binding to CD206-positive disease-associated macrophages. Should the partners achieve proof of concept, they expect to expand the collaboration to develop Manocept-linked Accurins as a novel approach of impacting the tumor microenvironment.
“We are pleased to work with BIND Therapeutics to explore the therapeutic potential of our two complementary technology platforms,” said Dr. Michael M. Goldberg, CEO of Macrophage Therapeutics and director of Navidea, in a press release. “The Manocept platform is the basis for the FDA- approved CD206-targeted sentinel lymph node detection agent Lymphoseek (technetium Tc 99m tilmanocept) injection. Coupled with BIND’s specifically engineered Accurins that concentrate therapeutic payloads to extracellular and intracellular compartments, with a tunable controlled-release profile, we are optimistic that we can create a wide range of therapeutic applications.”
BIND’s Accurins are targeted nanoparticles that offer prolonged circulation, controlled and tunable release and selective targeting of a therapeutic payload to diseased tissue or cells while avoiding the issues of immune surveillance detection and systemic toxicities. The Manocept platform is a proprietary mannose-containing, receptor- directed technology platform that can engineer novel, synthetic receptor-targeted imaging agents and therapeutics. Specifically, its properties make it possible to engineer novel immuno-constructs that can selectively bind to the mannose receptor CD206, as well as other C-type Lectins found on activated, disease-associated macrophages and tumor-associated macrophages. Disease-associated macrophages are known to play a primarily pro-tumoral role, in addition to being immunosuppressive.
“Tumor-activated or disease-associated macrophages are immune cells that play part of the role in the body’s defense against pathogens and tumor cells. They engulf unwanted cells and kill them per the direction of the immune system, but a lot of times—in cancer, for instance—those cells don’t do that; they actually confer protection of the tumor cells against the macrophages,” explains Andrew Hirsch, president and CEO of BIND Therapeutics. “And so we thought it was a very, very attractive cancer target to be able to target these activated macrophages. And then there’s a number of therapeutic approaches we can take once we target them, so this is really an idea of ‘Can we use their targeting platform and our Accurins to create a new therapeutic approach?’ It’s a bit of a departure for us from our traditional product development focus.”
Hirsch tells DDNews that Macrophage Therapeutics will provide the potential ligands for the deal while BIND provides its nanoparticle technology, adding that “Jointly we’re evaluating whether or not the Accurins actually target these activated macrophages by targeting CD206 and actually how do they target it: do the particles get inside, is it because they’re engulfed by the macrophages or is it because the actual ligand is pulling the particle into the cell by targeting CD206?”
“It is well established that macrophages play an important role in many disease states, but it has proven difficult to selectively target and alter macrophages that play a key role in disease progression,” Dr. Hagop Youssoufian, chief medical officer at BIND Therapeutics, commented. “By coupling Accurins with Macrophage’s well-credentialed CD206 targeting ligand, we may be able to treat macrophage-mediated diseases through increased uptake and concentration of targeted therapeutic payloads in the tumor microenvironment. BIND’s Medicinal Nanoengineering platform is able to combine multiple molecular components into a targeted, long-circulating Accurin. An Accurin nanoparticle that binds to CD206-positive macrophages could be a valuable asset in the armament against multiple cancers and disease states.”