Thermal-responsive Activation of Engineered Bacteria to Trigger Antitumor Immunity Post Microwave Ablation Therapy

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Dec 3

PMID 39627266

Authors

Yumin Wu

Bo Liu

Yifan Yan

Chuntao Gong

Kaiwei Wang

Nanhui Liu

Yujie Zhu

Maoyi Li

Chunjie Wang

Yizhe Yang

Liangzhu Feng

Zhuang Liu

Affiliations

Soon will be listed here.

Abstract

Incomplete tumor removal after microwave ablation (MWA), a widely used hyperthermia-based therapy, can result in tumor recurrence. Herein, attenuated Salmonella typhimurium VNP20009 is engineered to release interleukin-15&interleukin-15-receptor-alpha (IL-15&IL-15Rα) in response to mildly elevated temperature. Such 15&15R@VNP colonizes in tumors upon intravenous injection, and the expression of IL-15&IL-15Rα is triggered by MWA. Anti-tumor immune responses are elicited, efficiently suppressing tumor growth even after incomplete microwave ablation. We further design VNP20009 with thermal-responsive co-expression of both IL-15&IL-15Rα and soluble programmed cell death protein (sPD-1). Such sPD-1-15&15R@VNP can also reverse the functional suppression of immune cells driven by PD-1/PD-L1 axis, reinvigorating progenitor exhausted T cells, a critical subset of cytotoxic T lymphocytes responsive to immune checkpoint blockade. Such thermal-responsive engineered bacteria are thus a promising adjuvant therapy to potentiate tumor ablation therapies via effectively activating antitumor immunity.

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