Efficacy of Tumor-Targeting A1-R against Malignancies in Patient-Derived Orthotopic Xenograft (PDOX) Murine Models.

We developed tumor-targeting () A1-R, a facultative anaerobe that is an auxotroph of leucine and arginine. The tumor-targeting efficacy of 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 A1-R against recalcitrant cancers. 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 A1-R when combined with chemotherapeutic agents, molecular-targeting agents, or recombinant methioninase was also demonstrated. We suggest potential clinical uses of this A1-R treatment.