Setting "cold" tumors on fire: Cancer therapy with live tumor-targeting bacteria

Simin Manole; Dinh-Huy Nguyen; Jung-Joon Min; Shibin Zhou; Neil Forbes

doi:10.1016/j.medj.2024.11.002

Setting "cold" tumors on fire: Cancer therapy with live tumor-targeting bacteria

Med. 2025 Jan 10;6(1):100549. doi: 10.1016/j.medj.2024.11.002. Epub 2024 Dec 16.

Authors

Simin Manole¹, Dinh-Huy Nguyen², Jung-Joon Min³, Shibin Zhou⁴, Neil Forbes⁵

Affiliations

¹ Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA.
² Institute for Molecular Imaging and Theranostics, Chonnam National University, Hwasun, Jeonnam 58128, South Korea.
³ Institute for Molecular Imaging and Theranostics, Chonnam National University, Hwasun, Jeonnam 58128, South Korea; Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Jeonnam 58128, South Korea. Electronic address: jjmin@jnu.ac.kr.
⁴ Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: sbzhou@jhmi.edu.
⁵ Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA; Department of Chemical Engineering, University of Massachusetts, Amherst, MA, USA; Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA, USA; Department of Microbiology, University of Massachusetts, Amherst, MA, USA. Electronic address: forbes@umass.edu.

PMID: 39689707
DOI: 10.1016/j.medj.2024.11.002

Abstract

Immunotherapy with checkpoint blockade has shown remarkable efficacy in many patients with a variety of different types of cancer. However, the majority of patients with cancer have yet to benefit from this revolutionary therapy. Studies have shown that checkpoint blockade works best against immune-inflamed tumors characterized by the presence of tumor-infiltrating lymphocytes (TILs). In this review, we summarize studies using live tumor-targeting bacteria to treat cancer and describe various strategies to engineer the tumor-targeting bacteria for maximized immunoregulatory effects. We propose that tumor-localized infections by such engineered bacteria can create an immune microenvironment in favor of a more effective antitumor immunity with or without other therapies, such as immune checkpoint blockade (ICB). Finally, we will briefly outline some exemplary oncology clinical trials involving ICB plus live therapeutic bacteria, with a focus on their ability to modulate antitumor immune responses.

Publication types

Review

MeSH terms

Bacteria / drug effects
Bacteria / immunology
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Immunotherapy* / methods
Lymphocytes, Tumor-Infiltrating / drug effects
Lymphocytes, Tumor-Infiltrating / immunology
Neoplasms* / drug therapy
Neoplasms* / immunology
Neoplasms* / therapy
Tumor Microenvironment* / drug effects
Tumor Microenvironment* / immunology

Substances

Immune Checkpoint Inhibitors