Innovative Bacterial Therapy Targets Tumors Without Immune System Dependency

A groundbreaking study led by Professor Eijiro Miyako from the Japan Advanced Institute of Science and Technology (JAIST), in collaboration with Daiichi Sankyo Co., Ltd. and the University of Tsukuba, has introduced a novel bacterial-based cancer treatment utilizing a microbial consortium named AUN. Unlike traditional immunotherapies that rely heavily on the patient's immune system, this new approach demonstrates the ability to eradicate tumors independently of immune cell activation.

Historically, cancer immunotherapy traces its origins back to 1868 when German physician Busch reported a case where bacterial infection seemingly led to tumor regression. Subsequently, Dr. William Coley in 1893 proposed using bacteria as a therapeutic tool for cancer, laying the foundation for modern immunotherapies, including checkpoint inhibitors and CAR-T cell treatments. Although effective in many cases, these therapies depend on a functioning immune response, which can be compromised in patients undergoing chemotherapy or radiotherapy.

The innovative AUN therapy addresses this limitation by leveraging a collaboration between two naturally occurring bacteria:

• Proteus mirabilis (A-gyo), known for its tumor-resident properties
• Rhodopseudomonas palustris (UN-gyo), a photosynthetic bacterium

These bacteria work synergistically within the tumor microenvironment, inducing significant tumor destruction even in immunodeficient models. Remarkably, the therapy shows high biocompatibility, induces minimal side effects, and suppresses cytokine release syndrome (CRS), a common adverse effect of conventional immunotherapies.

The AUN bacteria execute multiple anti-cancer mechanisms, including the targeted destruction of tumor blood vessels and cancer cells, structural changes in A-gyo like filamentation stimulated by tumor metabolites, and a dynamic transformation of bacterial populations—initially a mixture of A-gyo and UN-gyo shifting predominantly to A-gyo within the tumor. The bacteria exhibit a regulatory partnership where UN-gyo modulates pathogenicity, preventing harmful side effects while boosting tumor-specific toxicity, a concept reminiscent of harmony in Japanese philosophy.

Dr. Miyako emphasized the potential impact of this research: "We are preparing to initiate clinical trials within the next six years and aim to bring bacteria-based cancer therapy to the broader market. This approach signifies a new chapter in cancer treatment, especially for patients with compromised immune systems."

Overall, this microbial alliance introduces a paradigm shift, providing a promising therapeutic avenue for immunocompromised patients and expanding the landscape of cancer treatment modalities beyond immune-dependent mechanisms.

Source: MedicalXpress