Abstract
We developed tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R, a facultative anaerobe that is an auxotroph of leucine and arginine. The tumor-targeting efficacy of S. typhimurium A1-R was demonstrated in vivo and vitro using several malignant cell lines including melanoma, sarcoma, glioma, breast, pancreatic, colon, cervical, prostate, and ovarian cancers. Our laboratory also developed a patient-derived orthotopic xenograft (PDOX) model by implanting patient-derived malignant tumor fragments into orthotopic sites in mice. We reviewed studies of S. typhimurium A1-R against recalcitrant cancers. S. typhimurium A1-R was effective against all PDOX tumor models tested and showed stronger efficacies than chemotherapy or molecular-targeting therapy against some tumors. Furthermore, the synergistic efficacy of S. typhimurium A1-R when combined with chemotherapeutic agents, molecular-targeting agents, or recombinant methioninase was also demonstrated. We suggest potential clinical uses of this S. typhimurium A1-R treatment.
Highlights
We review in the present report the therapeutic efficacy of S. typhimurium A1-R against malignancies in patient-derived orthotopic xenograft (PDOX) nude mouse models, in which human tumors are orthotopically implanted in mice, to examine future clinical applicability
In pancreatic cancer PDOX models, S. typhimurium A1-R had additional efficacy when combined with gemcitabine or cancer PDOXplus models, S. typhimurium had additional efficacy when combined with gemcitabine gemcitabine bevacizumab
The present review demonstrates the strong antitumor efficacy of S. typhimurium A1-R against recalcitrant-caner PDOX models, indicating advantages that S. typhimurium A1-R may have over chemotherapy
Summary
Coley began bacterial therapy of cancer using Streptococcus pyogenes (S. pyogenes) He developed Coley’s toxin, a mixture of killed S. pyogenes and Serratia marcescens, achieving clinical responses for many malignant tumors [1]. The immune-suppressive tumor microenvironment is conducive to bacteria, and host immune responses against administered bacteria may enhance antitumor immunity [3,4,5] These specific advantages in bacterial therapy can overcome the limit of traditional treatments, even exerting synergistic efficacy in combination with these treatments. Objective tumor response was not observed in any of these studies, several studies using S. typhimurium showed bacterial colonization in treated tumors after local or systemic administration [7]. We review in the present report the therapeutic efficacy of S. typhimurium A1-R against malignancies in patient-derived orthotopic xenograft (PDOX) nude mouse models, in which human tumors are orthotopically implanted in mice, to examine future clinical applicability
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