P01.07 Depletion of CD206high tumour-associated macrophages using a nanoconjugate limits tumour burden & dissemination in metastatic triple negative breast cancer in mice

Background Anti-inflammatory (M2) tumour-associated macrophages (TAMs) exert protumoural roles through angiogenesis, immunosuppression and resistance to therapies. 1 M2 TAMs express the mannose receptor, CD206, 2 excellent marker for targeted We have previously identified a peptide called mUNO that specifically binds CD206 on TAMs. Aiming dissect role of high in tumour progression immunosuppression, we depleted them using an doxorubicin (Adriamycin®)-containing polymer-drug nanoconjugate (St-PGA-DOX-mUNO, ‘OximUNO’) where polymer backbone is branched polyglutamic acid (St-PGA). 3 Materials Methods compared OximUNO with free DOX untargeted St-PGA-DOX. To study vitro cytotoxicity nanoconjugates, used M1 skewed derived from human blood buffy coat. vivo homing nanoconjugates orthotopic triple negative breast cancer (TNBC, 4T1 cells) model TNBC experimental metastases immunocompetent mice. For therapeutic efficacy studies, models TNBC, administered compounds intraperitoneally (i.p.). Results In vitro, showed 39% higher toxicity primary than St-PGA-DOX, 31% lower vivo, no change creatinine or alanine aminotransferase values, indicating toxic effects kidneys liver. Compared control St-PGA, i.p.-administered St-PGA-mUNO, improved both low accumulation treatment study, only significantly reduced volume 56% 38% less lung respectively. Additionally, St-PGA-DOX produced significant bodyweight loss whereas did not. Importantly, resulted 2-5-fold increase ratio CD8 + /FOXP3 expression, suggesting shift immune landscape towards immunostimulatory profile. model, monotherapy highest reduction metastases, this effect correlated TAMs; population was observed nanoconjugate. Conclusions Our data suggests elimination suppresses spontaneous safe manner, shifts could therefore be potential option patients. References Hughes R, Qian B-Z, Rowan C, Muthana M, Keklikoglou I, Olson OC, et al . Perivascular stimulate tumor relapse after chemotherapy. Cancer Res 2015; 75 (17):3479–91. Scodeller P, Simón-Gracia L, Kopanchuk S, Tobi A, Kilk K, Säälik Precision targeting binding peptide. Sci Rep 2017; 7 (1):14655. Duro-Castano Nebot VJ, Niño-Pariente Armiñán Arroyo-Crespo JJ, Paul Capturing ‘extraordinary’ soft-assembled charge-like polypeptides as strategy nanocarrier design. Adv Mater 29 (39):1702888. Disclosure Information A. Lepland: None. Malfanti: U. Haljasorg: S. Dordevic: L. Salumäe: P. Peterson: T. Teesalu: M.J. Vicent: Scodeller: