title: Salmonella typhimurium A1-R tumor targeting in immunocompetent mice is enhanced by a traditional Chinese medicine herbal mixture.
abstract: We have developed a bacterial cancer therapy strategy using the genetically-engineered strain Salmonella typhimurium A1-R (A1-R). A1-R is auxotrophic for leu and arg which attenuates bacterial growth in normal tissue but allows high tumor virulence. A1-R is effective against metastatic human and murine cancer cell lines in clinically-relevant nude-mouse models. However, A1-R treatment of tumors in immunocompetent mouse models with high doses is limited by toxicity. The current study evaluated a traditional Chinese medicine (TCM) herbal mixture in combination with A1-R therapy in a syngeneic metastatic immunocompetent mouse model of highly aggressive lung cancer. In a model of Lewis lung carcinoma, the combination of a TCM herbal mixture and S. typhimurium A1-R enabled bacteria to be safely administered at the large dose of 2 × 10(7) colony forming units once a week i.v. with increased treatment efficacy and reduced toxicity compared to monotherapy with A1-R. The herbal mixture prevented body weight loss, spleen weight gain and liver infection by A1-R, as well as hemorrhagic lesions on the skin, liver, and spleen, all observed with A1-R monotherapy. The results of the present study suggest that the combination of A1-R and TCM has important potential for therapy of highly aggressive types of cancer, including those which are resistant to standard therapy.
authors: AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111 USA.
authors: Yong
authors: Y
authors: Zhang
authors: Nan
authors: N
authors: Zhang
authors: Shibing
authors: S
authors: Su
authors: Robert M
authors: RM
authors: Hoffman
authors: Ming
authors: M
authors: Zhao
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007121:Immunocompetence; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014774:Virulence; D023041:Xenograft Model Antitumor Assays
keywords: C57/BL6 mice; GFP; Lewis lung carcinoma; RFP; Salmonella typhimurium A1-R; TCM; combination; tumor targeting