Chorobik Paulina, Marcinkiewicz Janusz
Department of Immunology, Jagiellonian University Medical College, Kraków, Poland.
Pol Arch Med Wewn. 2011 Dec;121(12):461-6.
In the course of evolution, bacteria from the genus Salmonella adapted to survive and multiply in a vertebrate host. Skillful use of bacterial interactions with the host immune system became the basis for the development of modified Salmonella-based therapeutic vaccines. Bacterial genome can be modified to reduce toxicity and to develop or enhance therapeutic activity. Salmonella-based therapeutic vaccines are an attractive and novel alternative for conventional cancer treatment (chemotherapy, radiotherapy, and passive immunotherapy). Live bacteria have the natural ability to sense external environment and penetrate the target tissue. Appropriate strains of Salmonella, infused into experimental animal tumor model, accumulate selectively in solid tumors and inhibit their growth. Moreover, the bacteria can reach tumor areas that are inaccessible for other, passively diffusing therapeutics, e.g., ischemic areas. Thus, bacteria can produce and locally release a natural or recombinant anticancer agent, which enhances their therapeutic effect. S. typhimurium VNP20009 strain is safe, which has been documented in clinical trials. However, the expected therapeutic benefit has not been observed, presumably due to insufficient tumor colonization by bacteria. To enhance colonization of solid tumors, VNP20009 bacteria have been equipped with the ability to express on the surface an antibody fragment specific for carcinoembryonic antigen present on human tumor cells. Additionally, to potentiate antitumor activity, the genetic material of VNP20009 has been engineered to overproduce an endogenous proapoptotic protein, which targets cancer and immune cells promoting tumor growth.
在进化过程中，沙门氏菌属的细菌逐渐适应在脊椎动物宿主体内存活和繁殖。巧妙利用细菌与宿主免疫系统的相互作用成为开发改良型沙门氏菌治疗性疫苗的基础。可以对细菌基因组进行改造以降低毒性，并开发或增强治疗活性。基于沙门氏菌的治疗性疫苗是传统癌症治疗（化疗、放疗和被动免疫疗法）的一种有吸引力的新型替代方案。活细菌具有感知外部环境并穿透靶组织的天然能力。将合适的沙门氏菌菌株注入实验动物肿瘤模型后，它们会选择性地在实体瘤中积聚并抑制其生长。此外，这些细菌能够到达其他被动扩散的治疗药物无法到达的肿瘤区域，例如缺血区域。因此，细菌可以产生并在局部释放天然或重组抗癌剂，从而增强其治疗效果。鼠伤寒沙门氏菌VNP20009菌株是安全的，这已在临床试验中得到证实。然而，尚未观察到预期的治疗益处，可能是由于细菌在肿瘤中的定殖不足。为了增强在实体瘤中的定殖，VNP20009细菌已具备在表面表达针对人类肿瘤细胞上存在的癌胚抗原的抗体片段的能力。此外，为了增强抗肿瘤活性，VNP20009的遗传物质已被改造以过量产生一种内源性促凋亡蛋白，该蛋白靶向促进肿瘤生长的癌细胞和免疫细胞。
