Oncolytic Probiotics with Molecular Pili for Solid Tumor Therapy.

2026-02-03
Advanced science (Weinheim, Baden-Wurttemberg, Germany) 13(19)

PubMed: 41632211
DOI: 10.1002/advs.202517989

Study Design

Population: mouse models of colorectal cancer and melanoma
Methods: selected a probiotic Lactobacillus rhamnosus (LR), designed molecular pili (MP) targeting collagen-rich solid tumors and modified them into LRs via chemical coupling (LR@MP); in mouse models, LR@MP was given at a safe dose of 4 × 10^5 CFU

Cell therapy and oncolytic viruses have emerged as promising cancer treatments but face significant challenges in solid tumors due to immune suppression and gene-related toxicities. Here, we selected a probiotic Lactobacillus rhamnosus (LR) that appears to exert oncolytic activity by inducing massive calcium influx, which subsequently triggers a lethal ROS burst in tumor cells. To reduce systemic toxicity and enhance oncolytic efficacy at the tumor site, we designed molecular pili (MP) targeting collagen-rich solid tumors and modified them into LRs via chemical coupling (LR@MP). In mouse models of colorectal cancer and melanoma, LR@MP increased intratumoral accumulation by two times and enhanced bacterial clearance from peripheral tissues. At a safe dose of 4 × 10⁵ CFU, LR@MP inhibited 60%-80% of tumor growth. This dual-optimization strategy provides a new approach for next-generation in vivo therapies and warrants further preclinical evaluation.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus rhamnosus Lr-32	—	Increased Intratumoral Accumulation	Beneficial	Moderate	View source LR@MP increased intratumoral accumulation by two times and enhanced bacterial clearance from peripheral tissues.
Lactobacillus rhamnosus Lr-32	—	Reduced Tumor Growth	Beneficial	Large	View source At a safe dose of 4 × 10<sup>5</sup> CFU, LR@MP inhibited 60%-80% of tumor growth.