Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model.
Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed-Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression-free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM-CSF. The safety and immune activating properties of ONCOS-102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS-102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS-102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti-tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti-tumor activity in the mesothelioma mouse model, ONCOS-102 was able to slow down tumor growth. Interestingly, a synergistic anti-tumor effect was seen when ONCOS-102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS-102 in combination with first-line chemotherapy in patients suffering from malignant mesothelioma.
Targovax Oy, Saukonpaadenranta 2, Helsinki, Finland.|Laboratory of ImmunoViroTherapy, Division of Pharmaceutical Biosciences and Centre for Drug Research (CDR), University of Helsinki, Viikinkaari 5, Helsinki, 00790, Finland.|Department of Virology, National Institute of Public Health-National Institute of Hygiene, Chocimska 24 Str, Warsaw, 00-791, Poland.
Lukasz
L
Kuryk
Targovax Oy, Saukonpaadenranta 2, Helsinki, Finland.
Elina
E
Haavisto
Laboratory of ImmunoViroTherapy, Division of Pharmaceutical Biosciences and Centre for Drug Research (CDR), University of Helsinki, Viikinkaari 5, Helsinki, 00790, Finland.
Mariangela
M
Garofalo
Laboratory of ImmunoViroTherapy, Division of Pharmaceutical Biosciences and Centre for Drug Research (CDR), University of Helsinki, Viikinkaari 5, Helsinki, 00790, Finland.
Cristian
C
Capasso
Laboratory of ImmunoViroTherapy, Division of Pharmaceutical Biosciences and Centre for Drug Research (CDR), University of Helsinki, Viikinkaari 5, Helsinki, 00790, Finland.
Mari
M
Hirvinen
Targovax Oy, Saukonpaadenranta 2, Helsinki, Finland.
Sari
S
Pesonen
Targovax Oy, Saukonpaadenranta 2, Helsinki, Finland.
Tuuli
T
Ranki
Oncos Therapeutics Oy, Saukonpaadenranta 2, Helsinki, Finland.
Lotta
L
Vassilev
Laboratory of ImmunoViroTherapy, Division of Pharmaceutical Biosciences and Centre for Drug Research (CDR), University of Helsinki, Viikinkaari 5, Helsinki, 00790, Finland.
Vincenzo
V
Cerullo
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology / Q000502:physiology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy* / Q000821:virology; D008654:Mesothelioma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy* / Q000821:virology; D000086002:Mesothelioma, Malignant; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy / Q000379:methods*; D000068437:Pemetrexed / Q000008:administration & dosage; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D000068437:Pemetrexed; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin
carboplatin; cisplatin; immunogenic cell death; mesothelioma; oncolytic adenovirus/ONCOS-102; pemetrexed