A chitosan hydrogel-based cancer drug delivery system exhibits synergistic antitumor effects by combining with a vaccinia viral vaccine.
Cancer treatment combining chemotherapy and immunotherapy has been vigorously exploited to further improve cancer therapeutic efficacy. This study investigated a new chemoimmunotherapy approach utilizing hydrogel as a local anti-cancer drug delivery system. Chitosan hydrogel containing doxorubicin (CH-DOX) and vaccinia virus vaccine expressing Sig/E7/LAMP-1 (Vac-Sig/E7/LAMP-1) were used as chemoimmunotherapeutic agents. It was found that intratumoral injection of CH-DOX effectively inhibited tumor growth itself and, in addition, exhibited a synergistic antitumor effect in combination with a vaccinia virus-based vaccine. This combination did not decrease but rather increased the number of tumor-specific CD8(+) T cells primed by vaccinia virus-mediated vaccination; the resulting antitumor effects were further improved up to 60 days as compared with monotherapy after tumor challenge, and the survival of tumor-bearing mice was dramatically prolonged. This study is a pioneer report that demonstrates the use of a biodegradable hydrogel system as an anti-cancer drug delivery system for successful chemoimmunotherapy. It is hoped that, this study can provide a foundation for a rational approach to improve antitumor efficacy of chemoimmunotherapy.
Han
Hee Dong
HD
Korea Research Institute of Chemical Technology,Yuseong, Daejeon 305-600, South Korea.
Song
Chung Kil
CK
Park
Yong Sung
YS
Noh
Kyung Hee
KH
Kim
Jin Hee
JH
Hwang
Taewon
T
Kim
Tae Woo
TW
Shin
Byung Cheol
BC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D048271:Chitosan / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D014611:Vaccination; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D014765:Viral Vaccines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D004317:Doxorubicin; D048271:Chitosan