We have previously developed mouse models of HER-2-positive
cervical cancer.
Tumors in nude mice had histological structures similar to the original
tumor and were stained by anti-HER-2 antibody in the same pattern as the patient's
cancer. We have also previously developed
tumor-targeting Salmonella typhimurium A1-R and have demonstrated its efficacy against patient-derived
tumor mouse models, both alone and in combination. In the current study, we determined the efficacy of S. typhimurium A1-R in combination with
trastuzumab on a patient-
cancer nude-mouse model of HER-2 positive
cervical cancer. Mice were randomized to 5 groups and treated as follows: (1) no treatment; (2) carboplatinum (30 mg/kg, ip, weekly, 5 weeks); (3)
trastuzumab (20 mg/kg, ip, weekly, 5 weeks); (4) S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks); (5) S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks) +
trastuzumab (20 mg/kg, ip, weekly, 5 weeks). All regimens had significant efficacy compared to the untreated mice. The relative
tumor volume of S. typhimurium A1-R +
trastuzumab-treated mice was smaller compared to
trastuzumab alone (p = 0.007) and S. typhimurium A1-R alone (p = 0.039). No significant
body weight loss was found compared to the no treatment group except for carboplatinum-treated mice (p = 0.021). Upon histological examination, viable
tumor cells were not detected, and replaced by stromal cells in the
tumors treated with S. typhimurium A1-R +
trastuzumab. The results of the present study suggest that S. typhimurium A1-R and
trastuzumab in combination are highly effective against HER-2-expressing
cervical cancer.