The growth of epithelial ovarian cancer, one of the most lethal malignancies, is associated with the presence of tumor-associated macrophages (TAMs), white blood cells that can block the anti-cancer activity of the immune system and immunotherapy.
Fortunately, TAMs can be “repolarized,” converted from immunosuppressive tumor-promoters to inflammatory tumor-fighters. Now, Fiona Yull, DPhil, Todd Giorgio, PhD, and colleagues have demonstrated an ingenious targeted approach to TAM repolarization using nanoparticles in a mouse model of ovarian cancer.
Given that TAMs overexpress a receptor for the sugar mannose, the researchers developed a “mannose-decorated” nanoparticle bearing a cargo of small, interfering RNA. TAMs preferentially bind to the nanoparticle and take in the siRNA, which then activates a signaling pathway that enhances the expression of proinflammatory genes.
Reporting in the journal BMC Cancer, the researchers show that intraperitoneal injection of the nanoparticles significantly reduced the tumor burden in the mice. These findings suggest a way forward to increase anti-tumor immunity in patients with this deadly form of cancer.
The research was supported by the National Institutes of Health (grants CA214043, CA239367, CA247202, CA217987), a 2018 Burroughs Wellcome Fund Physician-Scientist Institutional Award to Vanderbilt University, and a generous gift from Chris Hill through Anglo-American Charity Ltd.
