PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic T cell responses.
OX40 (CD134) is a tumor necrosis factor (TNF) receptor expressed mainly on activated T cells and transmits a potent costimulatory signal once engaged. Agonistic anti-OX40 monoclonal antibody (mAb) enhances tumor immune response leading to therapeutic effects in mouse tumor models. However, when tested in phase I clinical trials it did not show objective clinical activity in cancer patients. In this study, we examined the feasibility of nanoparticle (NP)-mediated delivery of anti-OX40 mAb to efficiently induce cytotoxic T lymphocyte (CTL) responses. The biodegradable poly(DL-lactide-co-glycolide) nanoparticle (PLGA-NP) carrying anti-OX40 mAb, anti-OX40-PLGA-NP, was prepared by double emulsion method and showed an average diameter of 86 nm with a loading efficiency of 25%. We found that anti-OX40-PLGA-NP induced CTL proliferation and tumor antigen-specific cytotoxicity as well as cytokine production more strongly than free anti-OX40 mAb. These results suggest that PLGA-based nanoparticle formulation may provide efficient delivery system of anti-OX40 mAb for cancer immunotherapy.
Laboratory of Immuno-Oncology, Department of Medical Oncology, Fujian Provincial Tumor Hospital, Fuzhou 350014, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China. Electronic address: mschen9401@aliyun.com.
Mingshui
M
Chen
Laboratory of Immuno-Oncology, Department of Medical Oncology, Fujian Provincial Tumor Hospital, Fuzhou 350014, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
Haichao
H
Ouyang
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350000, China.
Shangyong
S
Zhou
Laboratory of Immuno-Oncology, Department of Medical Oncology, Fujian Provincial Tumor Hospital, Fuzhou 350014, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
Jieyu
J
Li
Laboratory of Immuno-Oncology, Department of Medical Oncology, Fujian Provincial Tumor Hospital, Fuzhou 350014, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China. Electronic address: zjyunbin@189.cn.
Yunbin
Y
Ye
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000951:Antigens, Neoplasm / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017321:Clinical Trials, Phase I as Topic; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D007114:Immunization; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D053262:Receptors, OX40 / Q000819:agonists* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D016207:Cytokines; D053262:Receptors, OX40; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
Agonist anti-OX40 monoclonal antibody; Cytotoxic T lymphocytes; Nanoparticle; OX40; Poly(dl-lactide-co-glycolide)