Prospects for an SV40 vaccine

Our plain-English summary of Prospects for an SV40 vaccine, by M.J. Imperiale, H.I. Pass, M.G. Sanda (Seminars in Cancer Biology, 2001).

The study

• Authors: M.J. Imperiale, H.I. Pass, M.G. Sanda
• Journal: Seminars in Cancer Biology
• Published: 2001;11(1):81-5
• Type of article: Review
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The identification of SV40 as a possible cause of human cancer leads to the question of whether the unique properties of the virus can be exploited to treat patients with SV40-positive mesotheliomas, which are otherwise refractory to successful intervention. A modified SV40 T antigen, from which the transforming domains have been removed, has been cloned into a vaccinia virus vector and tested in animal tumor model systems. It has been shown to be effective against both subsequent tumor challenge and pre-existing tumors. Thus, the potential exists for use of such a vaccine in mesothelioma patients.

Copyright 2001 Academic Press.

In plain English

This article is a review, not a new study. It concerns the virus SV40, which the authors described as possibly involved in some human cancers, including mesothelioma. It does not discuss asbestos. The authors described a vaccine called vac-mTAg: a vaccinia virus carrying a shortened SV40 large T antigen (amino acids 205–562), with the parts linked to causing cancer removed. They summarized their earlier mouse experiments, which were published elsewhere. Vaccinated mice produced T cells that targeted the antigen. In BALB/c mice vaccinated and then given tumor cells, over one-third survived longer than 3 months, while all control mice died within 1 month. In mice injected with tumor cells before treatment, the vaccine plus interleukin-2 significantly increased survival times. The authors outlined a planned Phase I trial in patients with mesotheliomas that express the antigen, with an estimated 50 patients. The authors concluded that promising avenues exist for safe and effective SV40 vaccines. They noted that the modified antigen was still being tested to confirm that it cannot itself transform cells.

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: Review of the authors' own previously published and unpublished animal work on an SV40 vaccine, with a description of a planned Phase I clinical trial; no new data
• Who was studied: No new study population. The article reviews earlier experiments in BALB/c and C57Bl/6 mice (numbers not given) and describes a planned trial in patients with TAg-expressing mesotheliomas
• Exposure: Not asbestos. The vaccine vac-mTAg: a modified SV40 large T antigen (amino acids 205–562, with the pRb binding, J and p53 binding domains removed) cloned into a vaccinia virus vector
• Main results:
  • From the authors' earlier published work: vaccination stimulated T antigen-specific cytotoxic T cells in BALB/c and C57Bl/6 mice
  • From earlier work, in BALB/c mice vaccinated and then challenged with tumor cells 3 weeks later: over one-third of immunized mice survived longer than 3 months, while all control mice died within 1 month
  • From earlier work, in mice given tumor cells before treatment with vac-mTAg plus interleukin-2: survival times increased significantly
  • From an unpublished manuscript in preparation: vaccine-induced T cells cured up to 100% of tumor-bearing mice in a prostate cancer model
  • Planned (not yet done) Phase I trial: cohorts of six patients receiving escalating doses, with an estimated 50 patients accrued over 12–24 months
• The authors' conclusion: The authors concluded that promising avenues exist for safe and effective SV40 vaccines, and that antigen-specific immunotherapies may add to the experimental therapies available for SV40-induced disease
• Limitations the authors state:
  • The modified antigen was still being tested in cell culture to make sure it does not retain any ability to transform cells
  • Pre-existing immunity to vaccinia virus can affect responses to the vaccine, though the authors said it does not preclude its use

Topics

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

Medical terms in this study, explained in our Lexicon: SV40, Mesothelioma.

Related studies

• New molecular and epidemiological issues in mesothelioma: role of SV40 — M. Carbone, S. Fisher, et al. (1999)
• Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma — P. Rizzo, M. Carbone, et al. (1999)
• SV40 and the pathogenesis of mesothelioma — P. Rizzo, M. Bocchetta, et al. (2001)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Association of SV40 with human tumours — B. Jasani, A. Cristaudo, et al. (2001)
• Asbestos, Simian virus 40 and malignant mesothelioma — S.C. Stenton (1997)

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