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journal article·2026-04Open access

Oncolytic Probiotics with Molecular Pili for Solid Tumor Therapy

Haodong Ge, Chengsheng Ding, Xiao Yang, Si Gao, Changjie Yang, Yuchen Hou, Hongye Wang, Linke Bian, Hao Zhong, Yifan Qu, Luyang Zhang, Junjun Ma, Zhengwei Cai, Wenguo Cui, Minhua Zheng

Advanced Science· Volume 13· Issue 19
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Abstract

ABSTRACT 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 × 10 5 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.
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Research context

OpenAlex topics: Cancer Research and Treatments · Virus-based gene therapy research · Bacteriophages and microbial interactions

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai P. R. China

Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai P. R. China

Department of Biliary‐Pancreatic Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai P. R. China

Institute of Molecular Medicine (IMM) State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Department of Oncology Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai P. R. China

Department of Hepatobiliary Surgery The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei P. R. China

Shanghai Cancer Institute State Key Laboratory of Systems Medicine for Cancer Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai P. R. China

Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai P. R. China

Funding

National Natural Science Foundation of China

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