Research progress and clinical translation challenges in the use of oncolytic bacteria for cancer therapy.

Oncolytic bacteria represent a distinct group of microorganisms capable of selectively infecting and colonizing tumor tissues while sparing normal cells. They exert anti-tumor effects primarily by activating the host immune system and eliciting a robust anti-tumor immune response, which ultimately mediates tumor cell killing. According to their distinct mechanisms of action and target specificities, oncolytic bacteria are currently categorized into three main types: direct oncolytic bacteria, indirect oncolytic bacteria, and prophylactic oncolytic bacteria. However, the clinical translation of these therapies faces several challenges, including suboptimal immunogenicity and uneven spatiotemporal distribution in vivo, which hinder their broader application. This review systematically examines the primary bacterial species utilized in cancer therapy and addresses the key obstacles impeding their clinical translation. Our aim is to lay a theoretical foundation and offer a technical perspective for developing safer and more efficacious oncolytic bacterial strategies.