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.
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.
Oncos Therapeutics ; Helsinki, Finland.
Tuuli
T
Ranki
Docrates Cancer Center ; Helsinki, Finland.
Timo
T
Joensuu
Onkologie-Hämatologie; Krankenhaus Nordwest ; Frankfurt, Germany.
Elke
E
Jäger
Onkologie-Hämatologie; Krankenhaus Nordwest ; Frankfurt, Germany.
Julia
J
Karbach
Onkologie-Hämatologie; Krankenhaus Nordwest ; Frankfurt, Germany.
Claudia
C
Wahle
Docrates Cancer Center ; Helsinki, Finland.
Kalevi
K
Kairemo
Docrates Cancer Center ; Helsinki, Finland.
Tuomo
T
Alanko
Docrates Cancer Center ; Helsinki, Finland.
Kaarina
K
Partanen
Institute for Molecular Medicine Finland (FIMM) ; Helsinki, Finland.
Riku
R
Turkki
Institute for Molecular Medicine Finland (FIMM) ; Helsinki, Finland.
Nina
N
Linder
Institute for Molecular Medicine Finland (FIMM) ; Helsinki, Finland.
Johan
J
Lundin
Division of Pathology; HUSLAB and Haartman Institute; Helsinki University Central Hospital ; Helsinki, Finland ; Genome-Scale Biology; Research Programs unit; University of Helsinki ; Helsinki, Finland.
Ari
A
Ristimäki
Institute for Molecular Medicine Finland (FIMM) ; Helsinki, Finland.
Matti
M
Kankainen
Cancer Gene Therapy Group; Haartman Institute; University of Helsinki ; Helsinki, Finland.
Akseli
A
Hemminki
Oncos Therapeutics ; Helsinki, Finland.
Charlotta
C
Backman
Oncos Therapeutics ; Helsinki, Finland.
Kasper
K
Dienel
Oncos Therapeutics ; Helsinki, Finland.
Mikael
M
von Euler
Oncos Therapeutics ; Helsinki, Finland.
Elina
E
Haavisto
Oncos Therapeutics ; Helsinki, Finland.
Tiina
T
Hakonen
Oncos Therapeutics ; Helsinki, Finland.
Juuso
J
Juhila
Oncos Therapeutics ; Helsinki, Finland.
Magnus
M
Jaderberg
Oncos Therapeutics ; Helsinki, Finland.
Petri
P
Priha
Oncos Therapeutics ; Helsinki, Finland.
Lotta
L
Vassilev
Oncos Therapeutics ; Helsinki, Finland.
Antti
A
Vuolanto
Oncos Therapeutics ; Helsinki, Finland.
Sari
S
Pesonen
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