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

Our plain-English summary of 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, by T. Ranki, T. Joensuu, E. Jäger, et al (Oncoimmunology, 2014).

The study

• Authors: T. Ranki, T. Joensuu, E. Jäger, J. Karbach, C. Wahle, K. Kairemo, T. Alanko, K. Partanen, R. Turkki, N. Linder, J. Lundin, A. Ristimäki, M. Kankainen, A. Hemminki, C. Backman, K. Dienel, M. von Euler, E. Haavisto, T. Hakonen, J. Juhila, M. Jaderberg, P. Priha, L. Vassilev, A. Vuolanto, S. Pesonen
• Journal: Oncoimmunology
• Published: 2014;3(10):e958937
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This brief report described one patient, a 68-year-old man with asbestos-related malignant pleural mesothelioma that had kept progressing after two chemotherapy regimens and radiotherapy. The article did not describe his asbestos exposure. In a Phase I study he received nine injections of ONCOS-102 directly into the tumor. ONCOS-102 is a modified adenovirus carrying the immune-signaling gene GM-CSF. He also took oral cyclophosphamide, 50 mg a day. Side effects were grade 1 and 2, except for a grade 3 fever. A tumor biopsy taken 29 days after treatment began showed a 131-fold increase in CD8+ T-cells (immune cells that can kill cancer cells) compared with before treatment. Blood samples showed more CD8+ T-cells recognizing the tumor protein MAGE-A3. Tumor genes linked to cell-killing and Th1-type immunity were more active. PET imaging at 7.5 months showed a 47% fall in tumor metabolic activity compared with the 6-month scan. He survived 18 months from the start of treatment and over 33 months from diagnosis. The authors concluded that local ONCOS-102 treatment induced these immune responses, and they encouraged testing it with other immunotherapies. A single case cannot show how often this happens.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (brief report) of one patient treated in a Phase I study
• Who was studied: one 68-year-old man with asbestos-related malignant pleural mesothelioma, previously treated with cisplatin plus pemetrexed, docetaxel alone, and radiotherapy, and treated in a Phase I study (NCT01598129) approved by an ethics committee in Finland
• Exposure: The mesothelioma is described as asbestos-related, with no details of fiber type, job or dose. The treatment studied was intratumoral injections of ONCOS-102 (a GM-CSF-expressing oncolytic adenovirus) on days 1, 4, 8, 15, 29, 57, 85, 113 and 141, with 50 mg a day of oral cyclophosphamide.
• Main results:
  • In this patient, treatment caused grade 1 and 2 adverse events, except for a grade 3 fever
  • In the tumor biopsy taken 29 days after treatment began, CD8+ T-cells had increased 131-fold compared with the pre-treatment biopsy
  • In the patient's blood cells, MAGE-A3-specific CD8+ T-cells rose after treatment, seen 29 days after treatment began
  • In the post-treatment tumor sample, genes for the cytotoxic factors perforin, granzyme B and granulysin, and for the Th1-associated factors interferon gamma and IRF1, were more highly expressed
  • PET imaging at 7.5 months after treatment began showed a 47% decrease in total lesion glycolysis compared with the 6-month scan
  • The patient survived 18 months (542 days) from treatment initiation and over 33 months (999 days) from diagnosis
• The authors' conclusion: The authors concluded that local ONCOS-102 treatment induced dense infiltration of CD8+ T-cells into the tumor and systemic tumor-specific CD8+ T-cell responses. They said this encourages investigating ONCOS-102 in combination with other immunotherapies.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Tumor Microenvironment, Prognosis, Immunotherapy, Macrophage.

Related studies

• Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5/3-D24-GM-CSF) in peritoneal mesothelioma mouse model — L. Kuryk, A.W. Møller, et al. (2018)
• Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model — L. Kuryk, E. Haavisto, et al. (2016)
• Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies — M. Ried, T. Potzger, et al. (2013)
• Intratumoral macrophage phenotype and CD8+ T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma — R. Cornelissen, L.A. Lievense, et al. (2015)
• Local inflammatory response produced by solutions sterilized with asbestos type filters — R.S. Speirs, U. Wenck (1955)
• Antitumor activity of type III interferon alone or in combination with type I interferon against human non-small cell lung cancer — H. Fujie, T. Tanaka, et al. (2011)

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