Virulence-attenuated Salmonella engineered to secrete immunomodulators reduce tumour growth and increase survival in an autochthonous mouse model of breast cancer

Research output: Contribution to journalArticlepeer-review

Abstract

The ultimate goal of bacterial based cancer therapy is to achieve non-toxic penetration and colonisation of the tumour microenvironment. To overcome this efficacy-limiting toxicity of anticancer immunotherapy, we have tested a therapy comprised of systemic delivery of a vascular disrupting agent to induce intratumoral necrotic space, cannabidiol to temporarily inhibit angiogenesis and acute inflammation, and a strain of Salmonella Typhimurium that was engineered for non-toxic colonisation and expression of immunomodulators within the tumour microenvironment. This combination treatment strategy was administered to transgenic mice burdened with autochthonous mammary gland tumours and demonstrated a statistically significant 64% slower tumour growth and a 25% increase in mean survival time compared to control animals without treatment. These experiments were accomplished with minimal toxicity as measured by less than 7% weight loss and a return to normal weight gain within three days following intravenous administration of the bacteria. Thus, non-toxic, robust colonisation of the microenvironment was achieved to produce a significant antitumor effect.

Original languageEnglish (US)
Pages (from-to)430-438
Number of pages9
JournalJournal of Drug Targeting
Volume29
Issue number4
DOIs
StatePublished - 2021

Bibliographical note

Funding Information:
was provided by the Hubbard Broadcasting Foundation, ProjectStealth.org, and the ASL Cancer Research Fund.

Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Bacterial cancer therapy
  • anti-CTLA-4
  • anti-PD-L1
  • cancer immunotherapy
  • interleukin-15

PubMed: MeSH publication types

  • Journal Article

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