Enhanced efficacy of herpes simplex virus mutant HF10 combined with paclitaxel in peritoneal cancer dissemination models.
OBJECTIVE
Oncolytic viral therapy is used worldwide. Many genetically engineered viruses have been evaluated for their potential as a new therapeutic agent for cancer. HF10, herpes simplex virus (HSV) type-1 clone, has remarkable anti-tumor effects, based on our previous research. In this study, we investigated the ability of HF10 to infect and lyse murine colon cancer cells, CT26, in vitro, and tested its efficacy in an immuno-competent animal model of colorectal cancer. Further, we attempted to evaluate HF10/paclitaxel combination therapy.


METHODS
In vitro, viral replication and cytotoxicity of HF10 against CT26 was observed. In vivo, BALB/c mice harboring carcinomatous peritonitis of CT26 cells were treated with HF10, paclitaxel or HF10 combined with paclitaxel.


RESULTS
HF10 is effective for peritoneal dissemination without ascites. The combination of HF10 and paclitaxel prolonged survival of mice bearing carcinomatous dissemination of CT26 compared with the controls, HF10 alone and paclitaxel alone. Paclitaxel did not suppress viral replication and cytotoxicity of HF10.


CONCLUSIONS
These results indicate that the combination of HF10 and paclitaxel had a remarkable effect as a cancer therapy and this method is applicable to almost all advanced cancers. This new combination therapy is a potentially epoch-making cancer therapy.
Shimoyama
S
S
Department of Surgery II, Graduate School of Medicine Nagoya University, Nagoya, Japan.
Goshima
F
F
Teshigahara
O
O
Kasuya
H
H
Kodera
Y
Y
Nakao
A
A
Nishiyama
Y
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005822:Genetic Vectors / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy / Q000379:methods*; D017239:Paclitaxel / Q000627:therapeutic use; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D018139:Simplexvirus / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel