Speakers - CWC 2023

Abstract

Tumor tissue induces both hypoxic regions and poor vasculature, which limit the efficacy of conventional therapies. Bacteria-mediated cancer therapy can overcome some of the drawbacks of these treatments. Therefore, the clinical translation of bacterial therapies to treat disseminated or metastatic cancer is imperative. Here, we reported that updated YB1 (version 2.0), the first oxygen-regulated live bacterial drug-delivery vector for cancer immunotherapy, which is highly safe and effective, and has extensive expansibility. Preclinical murine studies demonstrate that treatment with a single intravenous dose of YB1 (version 1.0) can induce curative remission in tumor-bearing mice. Because of its super-carrying capacity, YB1 (version 2.0) can be further used as a super oncolytic delivery carrier. It can carry a variety of warheads for different tumors and combine with a variety of therapeutic antibodies, toxins, oncolytic viruses, and drugs to become a super oncolytic weapon. A large comparative oncology study was conducted to investigate the feasibility and tolerability of pet animals with spontaneous cancer in Hong Kong. Clinical translation of YB1 (version 2.0)-based therapy is dependent on the comprehensive assessment of clinical toxicities, bacterial shedding, pharmacokinetics, and clinical response in canines and felines with spontaneous cancer, which have comparable etiology, clinical progression, and response to therapy as human malignancies. In 2016, Noopy, the first pet dog with malignant sarcoma, was cured after YB1 (version 2.0) treatment. By 2022, the clinical study on pet animal cancer YB1 (version 2.0) had been completed, more than 100 pet animals with cancer had been enrolled, and Noopy had also achieved 5-year cancer-free survival. YB1 (version 2.0) can accurately target the hypoxia region of the tumor center, significantly shrank or completely lysed primary tumor and tumor metastases without damaging normal organs, while dogs showed no severe adverse reaction except some transient fever and nausea, demonstrating it is well-tolerated and safe in large animals with advanced or metastatic disease. Data from companion animal trials have informed clinical translation and showed that the first-in-class oncolytic bacteria, YB1 (version 2.0), featured with the ability of tumor-targeting and delivering destructive ‘warheads’, exhibits broad-spectrum antitumor activity and great potential for cancer therapy.