Development of Salmonella vaccines for cancer and viruses

沙门氏菌是几种不同的细菌之一，已被证明可以在实体肿瘤中定植，并被认为是细菌介导的抗肿瘤治疗发展的主要竞争者。活的重组减毒沙门氏菌可用于将蛋白质、DNA质粒或其他分子直接递送到实体肿瘤或肿瘤微环境中。沙门氏菌可以口服，生产成本低，可以引起粘膜和全身免疫反应。我们的目标是设计一种安全的减毒菌株，用于单独或与其他治疗（如化疗或免疫治疗）联合靶向实体肿瘤。为了初步筛选和鉴定鼠伤寒沙门菌的肿瘤定殖因子和菌株的发展，我们使用了一种特征良好的黑色素瘤模型，其中B16黑色素瘤细胞接种于同基因的C57BL6J小鼠菌株。由于缺乏功能性的Nramp1/SLC11A1， C57BL6J小鼠对鼠伤寒沙门氏菌感染高度敏感，我们也将使用Nramp1重组小鼠。减毒的鼠伤寒沙门氏菌菌株也将被用于将化疗或抗肿瘤分子（例如纳米体）直接输送到肿瘤中。一旦确定了有希望的沙门氏菌菌株，我们将测试小鼠体内转移的其他模型，包括人类肿瘤可以异种移植到小鼠体内的模型（与Alana Welm合作）。

Salmonella are one of several different bacteria that have been shown to colonize solid tumors and are considered a leading contender for the development of bacterial-mediated anti-tumor therapy. Live recombinant attenuated Salmonella can be used to deliver proteins, DNA plasmids or other molecules directly to solid tumors or the tumor microenvironment. Salmonella can be delivered orally, are inexpensive to produce and can elicit both mucosal and systemic immune responses. Our goal is to engineer a safe attenuated strain to target solid tumors either alone or in combination with other treatments such as chemotherapy or immunotherapy. For the initial screening and identification of Tumor Colonization Factors of Salmonella Typhimurium and strain development, we are using a well-characterized melanoma model in which B16 melanoma cells are inoculated in the syngeneic C57BL6J mouse strain. Since C57BL6J mice are highly susceptible to infection with Salmonella Typhimurium, due in part to the lack of functional Nramp1/SLC11A1, we will also use Nramp1 reconstituted mice. Attenuated Salmonella Typhimurium strains will also be adapted to deliver chemotherapy or anti-tumor molecules (e.g. nanobodies) directly to tumors. Once promising Salmonella strains have been identified we will test additional in vivo models for metastasis in mice, including a model where human tumors can be xenografted into mice (in collaboration with Alana Welm).