Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8+ T-cell response, prominent infiltration of CD8+ lymphocytes and Th1 type polarization

Oncoimmunology. 2014 Dec 15;3(10):e958937. doi: 10.4161/21624011.2014.958937. eCollection 2014 Nov.

Abstract

Late stage cancer is often associated with reduced immune recognition and a highly immunosuppressive tumor microenvironment. The presence of tumor infiltrating lymphocytes (TILs) and specific gene-signatures prior to treatment are linked to good prognosis, while the opposite is true for extensive immunosuppression. The use of adenoviruses as cancer vaccines is a form of active immunotherapy to initialise a tumor-specific immune response that targets the patient's unique tumor antigen repertoire. We report a case of a 68-year-old male with asbestos-related malignant pleural mesothelioma who was treated in a Phase I study with a granulocyte-macrophage colony‑stimulating factor (GM-CSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in prominent infiltration of CD8+ lymphocytes to tumor, marked induction of systemic antitumor CD8+ T-cells and induction of Th1-type polarization in the tumor. These results indicate that ONCOS-102 treatment sensitizes tumors to other immunotherapies by inducing a T-cell positive phenotype to an initially T-cell negative tumor.

Keywords: APC, antigen presenting cell; Adenovirus; CCL2, (C-Cmotif) ligand 2; CTCAE, common terminology criteria for adverse events; CX3CL1, (C-X3-C motif) ligand 1; CXCL10, (C-X-C motif) ligand 10; CXCL9, (C-X-C motif) ligand 9; ELISPOT, enzyme-linked immunospot assay; GM-CSF; GM-CSF, granulocyte macrophage colony stimulating factor; IFNg, interferon gamma; IRF1, interferon regulatory factor 1; PET, positron emission tomography; RANTES, regulated on activation, normal T cell expressed and secreted; TILs, tumor infiltrating lymphocytes; Th1 polarization; VP, viral particle; antitumor immunity; cytotoxic immunotherapy; tumor infiltrating lymphocytes.