Tangney Mark
David Geffen School of Medicine, University of California Los Angeles, 675 Charles E. Young Drive South, Los Angeles, California 90095, USA.
Discov Med. 2010 Sep;10(52):195-200.
The prime obstacle to achieving an effective treatment for cancer is that of eradicating tumors without harming healthy organs and cells of the patient. The concept of utilizing biological agents for delivery of therapeutic genes to patients to kill cancer cells has been under investigation for two decades, which exploits the natural ability of disease causing microbes to invade human cells. Safety-modified versions of pathogenic viruses or bacteria can deposit genes and induce production of anti-cancer agents upon administration to tumors and promising clinical trial successes have been achieved with various types of gene delivery vehicles. Bacteria present an attractive class of gene vectors, possessing a natural ability to grow specifically within tumors following intravenous (IV) injection. Several species such as Clostridium and Salmonella have been examined in clinical trials. However, as foreign, disease-causing bugs, their inherent toxicity has outweighed therapeutic responses in patients, despite efforts to reduce toxicity through genetic modification. A promising alternative exploits non-pathogenic bacterial species that have an existing natural relationship with humans. Our recent study (Cronin et al., 2010) has demonstrated that IV injection or ingestion of a species of probiotic bacterium, Bifidobacterium breve, in high numbers, results in trafficking of the bacteria throughout the body and accumulation specifically within cancerous tissue.
实现癌症有效治疗的主要障碍在于在不损害患者健康器官和细胞的情况下根除肿瘤。利用生物制剂将治疗性基因传递给患者以杀死癌细胞的概念已经研究了二十年，这利用了致病微生物侵入人体细胞的天然能力。对致病病毒或细菌进行安全改造的版本可以在给药至肿瘤后沉积基因并诱导抗癌剂的产生，并且使用各种类型的基因传递载体已经在临床试验中取得了有希望的成功。细菌是一类有吸引力的基因载体，静脉注射（IV）后具有在肿瘤内特异性生长的天然能力。几种细菌如梭菌和沙门氏菌已在临床试验中进行了研究。然而，作为外来的致病微生物，尽管通过基因改造努力降低毒性，但它们固有的毒性在患者中超过了治疗反应。一种有前途的替代方法利用与人类存在天然关系的非致病细菌物种。我们最近的研究（克罗宁等人，2010年）表明，静脉注射或大量摄入一种益生菌双歧杆菌会导致细菌在全身运输并特异性积聚在癌组织内。
