Antitumor effect of intratumoral administration of dendritic cell combination with vincristine chemotherapy in a murine fibrosarcoma model.
A new antitumor therapeutic strategy utilizing the combined effect of chemotherapy and DC (dendritic cell)-based immunotherapy was designed, and the effect of intratumoral injections of unpulsed, immature DCs was evaluated after in vivo pretreatment of vincristine on tumor growth in a murine fibrosarcoma tumor model. Vincristine exerted a much more potent apoptosis/necrosis-inducing effect on MCA-102 tumor cells than on DCs both in vitro and in vivo. Moreover, CD11c, CD40, CD80 and CD86 molecules on DCs were not downregulated after treatment with vincristine either in vitro or in vivo. The growth of tumor significantly regressed in the group which received the combined vincristine chemotherapy with intratumoral administration of DCs in contrast to the untreated group, the group treated with DCs alone, and the group treated with vincristine alone. In particular, an upregulated expression of CD40, CD80 and CD86 molecules on DCs was found in the combination treatment group. Furthermore, the number of CD4+ and CD8+ T cells and the staining intensity of their CD4 and CD8 surface molecules also increased after the combination treatment. Therefore, our results indicate the feasibility of this combination therapy with vincristine chemotherapy and DC-based immunotherapy as an efficient antitumor strategy for the treatment of fibrosarcoma.
Shin
J Y
JY
Department of Anatomy, College of Medicine, Pusan National University, Seo-Gu, Pusan, South Korea.
Lee
S K
SK
Kang
C D
CD
Chung
J S
JS
Lee
E Y
EY
Seo
S Y
SY
Lee
S Y
SY
Baek
S Y
SY
Kim
B S
BS
Kim
J B
JB
Yoon
S
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D017690:Cell Transplantation; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007167:Immunotherapy; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D010641:Phenotype; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D013778:Tetrazolium Salts; D013844:Thiazoles; D014750:Vincristine; C022616:thiazolyl blue