Academic News: The Scientific Research Team of Nanomedicine and Molecular Diagnosis and Treatment from Our State Key Laboratory Makes Significant Progress in Bacteria‐Based Tumor Immunotherapy
July 11, 2024
The chemotaxis and colonization of bacteria in tumor sites and their immunogenic properties make them ideal candidates for immunotherapy. Bacterial therapy has now emerged as one of the future directions in tumor immunotherapy. Photosynthetic bacteria (PSB) exhibit no toxic or pathogenic effects on test animals, no adverse influence on growth, and pose no potential hazards. Rich in essential nutrients like proteins, vitamins, and amino acids, PSB has been authorized by the Ministry of Agriculture of China for use as a feed additive, significantly improving the survival rates of animals and enhancing their resistance to disease.
Due to the favorable biosafety of PSB, the research team has undertaken extensive work in utilizing PSB for tumor immunotherapy. They first discovered that Rhodopseudomonas palustris in PSB demonstrates exceptional photothermal conversion performance. Leveraging its anaerobic and NIR chemotaxis properties, they achieved photothermal therapy on tumors (ACS Nano, 2021, 15(1): 1100-1110; CAS Q1, IF:18.0). Furthermore, they found that utilizing PSB as a hydrogen “manufactory” can continuously produce H2, enabling the killing of tumor cells through hydrogen-immune combination therapy (Journal of Nanobiotechnology, 2022, 20, 280; CAS Q1, IF:10.2). Based upon these works, they constructed engineered PSB capable of transporting tumor antigens (PSB-MAL) by modifying the PSB surface with maleimide (MAL) using membrane insertion technology, effectively inhibiting tumor growth and metastasis (ACS Nano, 2023, 17(19): 18716-18731; CAS Q1, IF=15.8). The components and functional variances of outer membrane vesicles (OMVs) derived from different sources of PSB impact their biological effects. It was found that in tumor models, both bacterium-derived outer membrane vesicles (OMVs) and bacteria-derived nanovesicles (BNVs) can polarize TAM and activate DC, enhancing antigen presentation ability. However, OMVs exhibited superior anti-tumor activity (Bioactive Materials, 2024, 36: 48-61; CAS Q1, IF:18.0). Given its natural lactic acid metabolism capacity, PSB holds promise as a “living drug” for lactate depletion, thus reprogramming the tumor immune microenvironment. However, the broad substrate metabolism of natural PSB severely limits its lactate metabolism capability and, consequently, the efficiency of reprogramming the tumor immune microenvironment. Based on this, the team developed a tailored culture medium through orthogonal trials to screen novel high-lactic acid metabolism photosynthetic bacteria LAB-1 that adapt to the tumor microenvironment. This approach enhances tumor immunotherapy by regulating the reprogramming of the tumor immune microenvironment (Advanced Materials, 2024, 2405930; CAS Q1, IF:27.4), providing a new strategy for tumor immunotherapy with important scientific significance.
The aforementioned work was completed through collaborative efforts between Professor Zhang Jinchao’s team from the College of Chemistry and Materials Science/State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei University and Researcher Li Zhenhua’s team from the Tenth Affiliated Hospital of Southern Medical University. It has received substantial support from the National Natural Science Foundation of China, Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province, and the Scientific Research and Innovation Team of Hebei University (Science and Technology).
Links to the papers:
[1]https://doi.org/10.1021/acsnano.0c08068
[2]https://doi.org/10.1186/s12951-022-01440-7
[3]https://doi.org/10.1021/acsnano.3c01912
[4]https://doi.org/10.1016/j.bioactmat.2024.02.025
[5]https://doi.org/10.1002/adma.202405930