Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5/3-D24-GM-CSF) in peritoneal mesothelioma mouse model

Our plain-English summary of Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5/3-D24-GM-CSF) in peritoneal mesothelioma mouse model, by L. Kuryk, A.W. Møller, M. Garofalo, et al (Journal of Medical Virology, 2018).

The study

• Authors: L. Kuryk, A.W. Møller, M. Garofalo, V. Cerullo, S. Pesonen, R. Alemany, M. Jaderberg
• Journal: Journal of Medical Virology
• Published: 2018;90(10):1669-1673
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Oncolytic adenoviral immunotherapy activates the innate immune system with subsequent induction of adaptive tumor-specific immune responses to fight cancer. Hence, oncolytic viruses do not only eradicate cancer cells by direct lysis, but also generate antitumor immune response, allowing for long-lasting cancer control and tumor reduction. Their therapeutic effect can be further enhanced by arming the oncolytic adenovirus with costimulatory transgenes and/or coadministration with other antitumor therapies. ONCOS-102 has already been found to be well tolerated and efficacious against some types of treatment-refractory tumors, including mesothelin-positive ovarian cancer (NCT01598129). It induced local and systemic CD8+ T-cell immunity and upregulated programmed death ligand 1. These results strongly advocate the use of ONCOS-102 in combination with other therapeutic strategies in advanced and refractory tumors, especially those expressing the mesothelin antigen. The in vivo work presented herein describes the ability of the oncolytic adenovirus ONCOS-102 to induce mesothelin-specific T-cells after the administration of the virus in bagg albino (BALB/c) mice with mesothelin-positive tumors. We also demonstrate the effectiveness of the interferon-γ the enzyme-linked immunospot (ELISPOT) assay to detect the induction of T-cells recognizing mesothelin, hexon, and E1A antigens in ONCOS-102-treated mesothelioma-bearing BALB/c mice. Thus, the ELISPOT assay could be useful to monitor the progress of therapy with ONCOS-102.

© 2018 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

In plain English

This was an animal experiment in mice testing the oncolytic adenovirus ONCOS-102 (Ad5/3-delta-24-GM-CSF) against peritoneal mesothelioma. The murine mesothelioma cell line AB12, which came from mesothelial cells of BALB/c mice given crocidolite asbestos by intraperitoneal injection and is positive for the mesothelin antigen, was implanted intraperitoneally (5x10(5) cells per 200 microlitres) into BALB/c mice, which were split into two groups, one treated with ONCOS-102 and the other with PBS, reported as n=6 mice without saying whether this was per group or in total. Repeated intraperitoneal injections of 1x10(11) viral particles per 200 microlitres were given on days 0, 3 and 6 after tumour formation, and tumours were measured on day 20. Spleen cells were then tested by IFN-gamma ELISPOT after stimulation with mesothelin, hexon and E1A peptide pools. Splenocytes from PBS-treated mice were negative for tumour antigen-specific T-cells, whereas ONCOS-102-treated mice showed T-cells against mesothelin, hexon and E1A. The authors concluded that ONCOS-102 induced systemic tumour-specific immunity and that the IFN-gamma ELISPOT assay could be useful for monitoring treatment with ONCOS-102.

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: animal experiment: ONCOS-102 given by repeated intraperitoneal injection (1x10(11) particles per 200 microlitres) on days 0, 3 and 6 versus PBS, with tumour measurement and IFN-gamma ELISPOT at day 20
• Who was studied: BALB/c mice bearing intraperitoneally implanted AB12 murine mesothelioma tumours, in two groups, one ONCOS-102-treated and one PBS-treated, stated as 'n=6 mice' (the article does not specify whether this is per group or in total); experiments done at the Biomedical Research Institute of Bellvitge (IDIBELL), Barcelona
• Exposure: Treatment exposure was the oncolytic adenovirus ONCOS-102 (Ad5/3-delta-24-GM-CSF) given intraperitoneally versus PBS; the AB12 tumour line itself originated from BALB/c mice exposed to crocidolite asbestos by intraperitoneal injection
• Main results:
  • Spleen cells from PBS (vehicle)-treated mice showed no tumour antigen-specific T-cells, while spleen cells from ONCOS-102-treated mice showed induction of tumour-specific T-cells
  • Mesothelin-specific T-cells were found at high frequency only in splenocytes of ONCOS-102-treated mice
  • T-cells against the viral hexon and E1A antigens were detected only in ONCOS-102-treated mice
  • Positive controls (PMA and ionomycin) gave high frequencies of IFN-gamma-secreting T-cells in both untreated and ONCOS-102-treated mice
  • The authors reported that ONCOS-102 treatment showed ability to control tumour growth compared with the control group (no numerical tumour volumes given in the text)
• The authors' conclusion: The authors concluded that repeated intraperitoneal ONCOS-102 treatment produced systemic tumour-specific immunity, including mesothelin-specific T-cells, and that the IFN-gamma ELISPOT assay could be used to monitor the efficacy and progress of ONCOS-102 treatment, alone or in combination.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Immunotherapy, Mesothelin, Ovarian Cancer, Mesothelioma.

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