Oncolytic bacteria therapy for malignant glioma

Malignant glioma is a group of primary malignant tumors of the central nervous system with an extremely poor prognosis, with glioblastoma being the most malignant type. Its highly invasive nature, tumor heterogeneity, stubborn immunosuppressive microenvironment, and the barrier effect of the blood-brain barrier result in limited efficacy of traditional surgery, radiotherapy, and chemotherapy, leading to high recurrence rates and short survival times. The tumor hypoxic microenvironment, as a core cause of treatment resistance and recurrence in glioma, also provides a natural therapeutic target for novel targeted therapies. Oncolytic bacteria, as an emerging tumor biotherapy technology, leverage natural tumor hypoxia targeting, autonomous proliferation capacity, multiple antitumor mechanisms, and flexible genetic modification potential. They can specifically colonize deep hypoxic areas of glioma, directly lyse tumor cells, remodel the tumor immune microenvironment, and overcome the bottleneck of drug delivery across the blood-brain barrier, making them a research hotspot for overcoming the challenges of glioma treatment. This article systematically reviews the core strain characteristics, antitumor molecular mechanisms, genetic engineering and synthetic biology modification strategies of oncolytic bacteria, summarizes preclinical research results and early clinical trial progress, deeply analyzes the core challenges currently faced in clinical translation, such as biosafety, delivery efficiency, and efficacy evaluation, and looks forward to future development directions combined with multidisciplinary cross-technologies, aiming to provide comprehensive theoretical support and practical references for deepening basic research and clinical translation of oncolytic bacteria in the field of malignant glioma.