The utility of poly(γ-glutamic acid) nanoparticles as antigen delivery carriers in dendritic cell-based cancer immunotherapy.
Cytotoxic T-lymphocytes (CTLs) specific for tumor-associated antigens (TAAs) act in the immune surveillance system as major effector cells to eliminate malignant cells. Immunization with TAA-loaded dendritic cells (DCs) has great potential for treating cancer, because DCs are potent antigen-presenting cells capable of inducing antigen-specific CTLs by the primary activation of naive T-lymphocytes. The establishment of a non-cytotoxic and efficient antigen delivery method is required to improve the efficacy of DC-based cancer immunotherapy. We developed biodegradable poly(γ-glutamic acid) nanoparticles (γ-PGA NPs) that can efficiently entrap various proteins as antigen delivery carriers. γ-PGA NPs efficiently delivered entrapped antigenic proteins into DCs without cytotoxicity and presented antigens to DCs via major histocompatibility complex class I and II molecules. Immunization with TAA-loaded DCs using γ-PGA NPs inhibited tumor growth by inducing TAA-specific CTLs. These findings indicate that γ-PGA NPs can function as useful antigen delivery carriers in DC-based cancer immunotherapy.
Department of Biotechnology and Therapeutics, Osaka University, Japan.
Keisuke
K
Matsuo
Yumiko
Y
Ishii
Kazuhiko
K
Matsuo
Tomoyo
T
Yoshinaga
Mitsuru
M
Akashi
Yohei
Y
Mukai
Yasuo
Y
Yoshioka
Naoki
N
Okada
Shinsaku
S
Nakagawa
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D003713:Dendritic Cells; D004337:Drug Carriers; D005260:Female; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives*; D013601:T-Lymphocytes / Q000378:metabolism
D000941:Antigens; D004337:Drug Carriers; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid