Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8⁺ T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer

References

• Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348:203-13; PMID:12529460; http://dx.doi.org/10.1056/NEJMoa020177
   PubMed Web of Science ®Google Scholar
• Tomsova M, Melichar B, Sedlakova I, Steiner I. Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol 2008; 108:415-20; PMID:18037158; http://dx.doi.org/10.1016/j.ygyno.2007.10.016
   PubMed Web of Science ®Google Scholar
• Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 2005; 102:18538-43; PMID:16344461; http://dx.doi.org/10.1073/pnas.0509182102
   PubMed Web of Science ®Google Scholar
• Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004; 10:942-9; PMID:15322536; http://dx.doi.org/10.1038/nm1093
   PubMed Web of Science ®Google Scholar
• Duraiswamy J, Freeman GJ, Coukos G. Therapeutic PD-1 pathway blockade augments with other modalities of immunotherapy T-cell function to prevent immune decline in ovarian cancer. Cancer Res 2013; 73:6900-12; PMID:23975756; http://dx.doi.org/10.1158/0008-5472.CAN-13-1550
   PubMed Web of Science ®Google Scholar
• Ascierto PA. Immunotherapies and novel combinations: the focus of advances in the treatment of melanoma. Cancer Immunol Immunother 2014; 64:271-4
   Web of Science ®Google Scholar
• Lavoué V, Thédrez A, Levêque J, Foucher F, Henno S, Jauffret V, Belaud-Rotureau MA, Catros V, Cabillic F. Immunity of human epithelial ovarian carcinoma: the paradigm of immune suppression in cancer. J Transl Med 2013; 11:147; PMID:23763830; http://dx.doi.org/10.1186/1479-5876-11-147
   PubMed Web of Science ®Google Scholar
• Webb JR, Milne K, Nelson BH. Location, location, location: CD103 demarcates intraepithelial, prognostically favorable CD8+ tumor-infiltrating lymphocytes in ovarian cancer. Oncoimmunol 2014; 3:e27668; PMID:25101220; http://dx.doi.org/10.4161/onci.27668
   PubMedGoogle Scholar
• Daudi S, Eng KH, Mhawech-Fauceglia P, Morrison C, Miliotto A, Beck A, Matsuzaki J, Tsuji T, Groman A, Gnjatic S, et al. Expression and immune responses to MAGE antigens predict survival in epithelial ovarian cancer. PloS One 2014; 9:e104099; PMID:25101620
   PubMedGoogle Scholar
• Kayser S, Watermann I, Rentzsch C, Weinschenk T, Wallwiener D, Guckel B. Tumor-associated antigen profiling in breast and ovarian cancer: mRNA, protein or T cell recognition? J Cancer Res Clin Oncol 2003; 129:397-409; PMID:12836015; http://dx.doi.org/10.1007/s00432-003-0445-7
   PubMed Web of Science ®Google Scholar
• Raspollini MR, Castiglione F, Rossi Degl'innocenti D, Amunni G, Villanucci A, Garbini F, Baroni G, Taddei GL. Tumour-infiltrating gamma/delta T-lymphocytes are correlated with a brief disease-free interval in advanced ovarian serous carcinoma. Ann Oncol 2005; 16(4):590-6; PMID:15699022; http://dx.doi.org/10.1093/annonc/mdi112
   PubMed Web of Science ®Google Scholar
• Shiver JW, Fu T-M, Chen L, Casimiro DR, Davies M-E, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, et al. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 2002; 415:331-5; PMID:11797011; http://dx.doi.org/10.1038/415331a
   PubMed Web of Science ®Google Scholar
• Draper S, Heeney J. Viruses as vaccine vectors for infectious diseases and cancer. Nature Rev Microbiol 2010; 8:62-73; PMID:19966816; http://dx.doi.org/10.1038/nrmicro2240
   PubMed Web of Science ®Google Scholar
• Bart P-A, Huang Y, Karuna S, Chappuis S, Gaillard J, Kochar N, Shen X, Allen MA, Ding S, Hural J, et al. HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial. J Clin Invest 2014; 124(11):4843-56; PMID:25271627; http://dx.doi.org/10.1172/JCI75894
   PubMed Web of Science ®Google Scholar
• Koski A, Kangasniemi L, Escutenaire S, Pesonen S, Cerullo V, Diaconu I, Nokisalmi P, Raki M, Rajecki M, Guse K, et al. Treatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF. Mol Ther 2010; 18:1874-84; PMID:20664527; http://dx.doi.org/10.1038/mt.2010.161
   PubMed Web of Science ®Google Scholar
• Dranoff G. GM-CSF based cancer vaccines. Immunol Rev 2002; 188:147-154; PMID:12445288; http://dx.doi.org/10.1034/j.1600-065X.2002.18813.x
   PubMed Web of Science ®Google Scholar
• van der Laar L, Coffer PJ, Woltman AM. Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. Blood 2012; 119:3383-3393; PMID:22323450; http://dx.doi.org/10.1182/blood-2011-11-370130
   PubMedGoogle Scholar
• Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol 2014; 27:1-7; PMID:24413387; http://dx.doi.org/10.1016/j.coi.2013.12.005
   PubMed Web of Science ®Google Scholar
• Ghiringelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 2007;56:641-648; PMID:16960692; http://dx.doi.org/10.1007/s00262-006-0225-8
   PubMedGoogle Scholar
• Cerullo V, Diaconu I, Kangasniemi L, Rajecki M, Escutenaire S, Koski A, Romano V, Rouvinen N, Tuuminen T, Laasonen L, et al. Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus. Mol Ther 2011; 19:1737-46; PMID:21673660; http://dx.doi.org/10.1038/mt.2011.113
   PubMed Web of Science ®Google Scholar
• Brune IB, Wilke W, Hensler T, Holzmann B, Siewert JR. Downregulation of T helper type 1 immune response and altered pro-inflammatory and anti-inflammatory T cell cytokine balance following conventional but not laparoscopic surgery. Am J Surg 1999; 177:55-60; PMID:10037309; http://dx.doi.org/10.1016/S0002-9610(98)00299-2
   PubMed Web of Science ®Google Scholar
• Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313:1960-4; PMID:17008531; http://dx.doi.org/10.1126/science.1129139
   PubMed Web of Science ®Google Scholar
• Galon J, Pages F, Marincola FM, Thurin M, Trinchieri G, Fox BA, Gajewski TF, Ascierto PA. The immune score as a new possible approach for the classification of cancer. J Rranslat Med 2012; 10:1-4; PMID:22214470; http://dx.doi.org/10.1186/1479-5876-10-1
   PubMed Web of Science ®Google Scholar
• Frierson HF Jr, Moskaluk CA, Powell SM, Zhang H, Cerilli LA, Stoler MH, Cathro H, Hampton GM. Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas. Hum Pathol 2003; 34:605-609; PMID:12827615; http://dx.doi.org/10.1016/S0046-8177(03)00177-1
   PubMed Web of Science ®Google Scholar
• Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515:568-571; PMID:25428505; http://dx.doi.org/10.1038/nature13954
   PubMed Web of Science ®Google Scholar