title: PolyI:C and CpG Synergize with Anti-ErbB2 mAb for Treatment of Breast Tumors Resistant to Immune Checkpoint Inhibitors.
abstract: Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs, such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab, and patients have a worse prognosis. Because type I and II IFNs are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long-lasting CD8+T cell-dependent antitumor immunity. Remarkably, polyI:C and CpG was superior to combined PD-1/CTLA-4 blockade in sensitizing tumors to anti-ErbB2 mAb therapy. Local injection of CpG and polyI:C in a primary tumor significantly enhanced the activity of systemic anti-ErbB2 mAb against a distant untreated tumor. Type I and II IFNs, as well as natural killer cells and CD8+T cells, were indispensible to the synergistic activity of the combination treatment. Because synthetic RNA analogues and CpG oligodeoxynucleotides have been safely used in clinical trials, our study supports combination treatments with anti-ErbB2 mAbs. Cancer Res; 77(2); 312-9. ©2016 AACR.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.|Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Charlebois
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.|Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Québec, Canada.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Allard
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.|Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Québec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Allard
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.|Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Québec, Canada.|Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.|Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Buisseret
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.|Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Québec, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Turcotte
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.|Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Québec, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pommey
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.|Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Québec, Canada.
authors.forename: Pavel
authors.initials: P
authors.lastname: Chrobak
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. john.stagg@umontreal.ca.|Institut du Cancer de Montréal, Montréal, Québec, Canada.|Faculté de Pharmacie, Université de Montréal, Québec, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Stagg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D005260:Female; D007369:Interferon Inducers / Q000276:immunology / Q000494:pharmacology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology*; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D007369:Interferon Inducers; D009838:Oligodeoxyribonucleotides; D011070:Poly I-C; D061026:Programmed Cell Death 1 Receptor; D018719:Erb-b2 Receptor Tyrosine Kinases; C408982:CPG-oligonucleotide; C491383:Pdcd1 protein, mouse; C524056:Erbb2 protein, mouse