Nanoparticles built by self-assembly of amphiphilic gamma-PGA can deliver antigens to antigen-presenting cells with high efficiency: a new tumor-vaccine carrier for eliciting effector T cells.
Nanotechnology is a fundamental technology for designing and generating innovative carriers for biomacromolecular drugs. Biodegradable poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent vaccine carriers capable of delivering antigenic proteins to antigen-presenting cells (APCs) and eliciting potent immune responses based on antigen-specific cytotoxic T lymphocytes. In mice, subcutaneous immunization with gamma-PGA NPs entrapping ovalbumin (OVA) more effectively inhibited the growth of OVA-transfected tumors than immunization with OVA emulsified using Freund's complete adjuvant. In addition, gamma-PGA NPs did not induce histopathologic changes after subcutaneous injection or acute toxicity through intravenous injection. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins into APCs, and these antigen-capturing APCs migrated to regional lymph nodes. Our results demonstrate that a gamma-PGA NP system for antigen delivery will advance the clinical utility of vaccines against cancer.
Yoshikawa
Tomoaki
T
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Okada
Naoki
N
Oda
Atsushi
A
Matsuo
Keisuke
K
Matsuo
Kazuhiko
K
Kayamuro
Hiroyuki
H
Ishii
Yumiko
Y
Yoshinaga
Tomoyo
T
Akagi
Takami
T
Akashi
Mitsuru
M
Nakagawa
Shinsaku
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D045744:Cell Line, Tumor; D004337:Drug Carriers; D005620:Freund's Adjuvant / Q000494:pharmacology; D007150:Immunohistochemistry; D007167:Immunotherapy; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011099:Polyglutamic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015203:Reproducibility of Results; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004337:Drug Carriers; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D010047:Ovalbumin; D005620:Freund's Adjuvant