Michán Carmen, Prados José, Ramos Juan-Luis
Departamento de Bioquímica y Biología Molecular, Campus de Excelencia Internacional Agroalimentario CeiA3, Universidad de Córdoba, Córdoba, Spain.
Department of Anatomy and Embryology, Faculty of Medicine, Center of Biomedical Research (CIBM), Instituto de Investigación Biosanitaria (IBS) de Granada; Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain.
Microb Biotechnol. 2025 Jan;18(1):e70090. doi: 10.1111/1751-7915.70090.
The discovery at the end of the 20th century of genes that induce cell death revolutionised the biocontaintment of genetically manipulated bacteria for environmental or agricultural applications. These bacterial 'killer' genes were then assayed for their potential to target and control malignant cells in human cancers. The identification of the bacteriomes in different human organs and tissues, coupled with the observation that bacteria tend to accumulate near tumours, has opened new avenues for anti-cancer strategies. This progress, along with recent insights into how cancer cells evade immune response, has prompted innovative therapeutic approaches. Tumour microenvironments are typically nutrient-rich, characterised by low oxygen tensions and very resistant to immune responses. Two recent studies in MBT highlight the promise of using Salmonella typhimurium and Escherichia coli as vectors in novel cancer treatments. Engineered S. typhimurium strains can generate adjuvant flagellin-antigen complexes that function as in situ vaccines, hence increasing the immunogenic responses within tumour environment. Similarly, gut E. coli can be used as vectors to targert tumour cells in colon cancer, enabling both diagnostic applications and localised treatments. Both approaches hold significant potential to improve patient survival outcomes.
20世纪末发现的诱导细胞死亡的基因,彻底改变了用于环境或农业应用的基因工程改造细菌的生物防护。随后对这些细菌“杀手”基因靶向和控制人类癌症恶性细胞的潜力进行了检测。不同人体器官和组织中细菌群落的鉴定,以及细菌倾向于在肿瘤附近聚集的观察结果,为抗癌策略开辟了新途径。这一进展,连同最近对癌细胞如何逃避免疫反应的见解,促使了创新治疗方法的出现。肿瘤微环境通常营养丰富,其特点是氧分压低且对免疫反应极具抗性。《分子与细胞肿瘤学》最近的两项研究突出了将鼠伤寒沙门氏菌和大肠杆菌用作新型癌症治疗载体的前景。工程化的鼠伤寒沙门氏菌菌株可以产生作为原位疫苗发挥作用的佐剂鞭毛蛋白 - 抗原复合物,从而增强肿瘤环境中的免疫原性反应。同样,肠道大肠杆菌可用作靶向结肠癌肿瘤细胞的载体,实现诊断应用和局部治疗。这两种方法在改善患者生存结果方面都具有巨大潜力。