PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic T cell responses

被引：79

作者：

Chen, Mingshui ^{[1
,2
]}

Ouyang, Haichao ^{[1
,2
]}

Zhou, Shangyong ^{[3
]}

Li, Jieyu ^{[1
,2
]}

Ye, Yunbin ^{[1
,2
]}

机构：

[1] Fujian Prov Tumor Hosp, Dept Med Oncol, Lab Immunooncol, Fuzhou 350014, Peoples R China

[2] Fujian Prov Key Lab Translat Canc Med, Fuzhou 350014, Peoples R China

[3] Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fuzhou 350000, Peoples R China

来源：

CELLULAR IMMUNOLOGY | 2014年 / 287卷 / 02期

关键词：

OX40; Agonist anti-OX40 monoclonal antibody; Cytotoxic T lymphocytes; Poly(DL-lactide-co-glycolide); Nanoparticle; TUMOR-NECROSIS-FACTOR; OX40; LIGAND; IN-VIVO; CANCER-IMMUNOTHERAPY; CLONAL EXPANSION; KAPPA-B; MEMORY; SURVIVAL; ACTIVATION; EXPRESSION;

D O I：

10.1016/j.cellimm.2014.01.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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(m-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. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：91 / 99

页数：9

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