Dendritic cells loaded with exogenous antigen by electroporation can enhance MHC class I-mediated antitumor immunity.
To develop an efficient antitumor immunotherapy, we have examined if dendritic cells (DCs) loaded with soluble antigens by electroporation present more antigens via the MHC (major histocompatibility complex) class I pathway, which mediate a cytotoxic T-cell response. DCs loaded with ovalbumin (OVA) by electroporation presented more MHC class I-restricted determinants compared with DCs pulsed with OVA. When electroporated DCs were pulsed with OVA for additional times, both MHC class I- and II-restricted presentation of OVA were increased compared with each single procedure, including electroporation or simple pulse. Immunization with DCs loaded with OVA by electroporation induced higher cytotoxicity of splenocytes to E.G7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with DCs pulsed with OVA. In the animal study, immunization with DCs loaded with OVA or tumor cell lysates by electroporation induced an effective antitumor immunity against tumor of E.G7 cells or Lewis lung carcinoma cells, respectively. In addition, immunization with DCs loaded with antigen by combination of electroporation and pulse, completely protected mice from tumor formation, and prolonged survival, in both tumor models. These results demonstrated that electroporation would be a useful way to enhance MHC class I-mediated antitumor immunity without functional deterioration, and that the combination of electroporation and pulse could be a simple and efficient antigen-loading method and consequently lead to induction of strong antitumor immunity.
Kim
Kwang-Woon
KW
Department of Biochemistry, College of Medicine, Pusan National University, 602-739 Pusan, Korea.
Kim
Sun-Hee
SH
Jang
Jung-Hee
JH
Lee
Eun-Yup
EY
Park
Soon-Won
SW
Um
Jee-Hyun
JH
Lee
Yun-Jung
YJ
Lee
Chang-Hun
CH
Yoon
Sik
S
Seo
Su-Yeong
SY
Jeong
Min-Ho
MH
Lee
Seong-Tae
ST
Chung
Byung-Seon
BS
Kang
Chi-Dug
CD
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D018274:Electroporation; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007114:Immunization; D016219:Immunotherapy, Adoptive; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D010047:Ovalbumin