Skip Ackerman Center for Molecular Therapeutics, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Methods Mol Biol. 2021;2323:267-280. doi: 10.1007/978-1-0716-1499-0_19.
Spontaneous tumor regression following bacterial infection has been observed for hundreds of years. These observations along with anecdotal medical findings in 1890s led to the development of Coley's "toxins," consisting of killed Streptococcus pyogenes and Serratia marcescens bacteria, as the first cancer immunotherapy. The use of this approach, however, was not widely accepted at the time especially after the introduction of radiation therapy as a treatment for cancer in the early 1900s. Over the last 30-40 years there has been renewed interest in the use of bacteria to treat human solid tumors. This is based on the observation that various nonpathogenic anaerobic bacteria can infiltrate and replicate within solid tumors when given intravenously. Bacteria tested as potential anticancer agents include the Gram-positive obligate anaerobes Bifidobacterium and Clostridium, as well as the gram-negative facultative anaerobe Salmonella. Recent advances in synthetic biology and clinical success in cancer immunotherapy provide renewed momentum for developing bacteria-based cancer immunotherapy for cancer treatment and should allow greater potential for the development of novel therapeutic approaches for this devastating disease.
数百年来,人们已经观察到细菌感染后肿瘤的自发消退。这些观察结果以及 19 世纪的一些医学发现,促使 Coley 开发了“毒素”,其中包括死的化脓性链球菌和粘质沙雷氏菌,作为第一种癌症免疫疗法。然而,当时这种方法并没有被广泛接受,尤其是在 1900 年代初放射疗法作为癌症治疗方法引入之后。在过去的 30-40 年中,人们对使用细菌治疗人类实体瘤重新产生了兴趣。这是基于这样一种观察,即各种非致病性厌氧菌在静脉内给予时可以渗透和复制到实体瘤中。作为潜在抗癌药物测试的细菌包括革兰氏阳性专性厌氧菌双歧杆菌和梭菌,以及革兰氏阴性兼性厌氧菌沙门氏菌。合成生物学的最新进展和癌症免疫疗法的临床成功为开发基于细菌的癌症免疫疗法治疗癌症提供了新的动力,并应为这种毁灭性疾病开发新的治疗方法提供更大的潜力。