Enhanced antitumor immunity by targeting dendritic cells with tumor cell lysate-loaded chitosan nanoparticles vaccine.
Whole tumor cell lysates (TCL) have been implemented as tumor antigens for cancer vaccine development, although clinical outcomes of TCL-based antitumor immunotherapy remain unsatisfactory. In order to improve the efficacy of TCL-based vaccines, biomaterials have been employed to enhance antigen delivery and presentation. Here, we have developed chitosan nanoparticles (CTS NPs) with surface mannose (Man) moieties for specific dendritic cells (DCs) targeting (Man-CTS NPs). The Man-CTS NPs were then loaded with TCL generated from B16 melanoma cells (Man-CTS-TCL NPs) for in vitro and in vivo assessment. Potency of the Man-CTS-TCL NPs as cancer vaccine was also assessed in vivo by immunization of mice with Man-CTS-TCL NPs followed by re-challenge with B16 melanoma cell inoculation. We have shown here that Man-CTS-TCL NPs promote bone marrow-derived dendritic cells (BMDCs) maturation and antigen presentation in vitro. In vivo evaluation further demonstrated that the Man-CTS-TCL NPs were readily taken up by endogenous DCs within the draining lymph node (DLN) following subcutaneous administration accompanied by increasing in serum IFN-γ and IL-4 levels. Tumor growth was also significantly delayed in mice primed with Man-CTS-TCL NPs vaccine, attributable at least in part to cytotoxic T lymphocytes response. Moreover, Man-CTS-TCL NPs vaccine also exhibited therapeutic effects in mice with melanoma. Thus, we report here the Man-CTS-TCL NPs as effective anti-tumor vaccine for cancer immunotherapy.
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Gao-Na
GN
Shi
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Chuang-Nian
CN
Zhang
Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, L69 7BE, UK.
Rong
R
Xu
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 300353, China.
Jin-Feng
JF
Niu
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Hui-Juan
HJ
Song
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Xiu-Yuan
XY
Zhang
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Wei-Wei
WW
Wang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 300353, China.
Yan-Ming
YM
Wang
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. Electronic address: cli0616826@126.com.
Chen
C
Li
Cardiff Institute of Tissue Engineering & Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, UK. Electronic address: weiX1@cardiff.ac.uk.
Xiao-Qing
XQ
Wei
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China; Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, China. Electronic address: kongdeling@nankai.edu.cn.
De-Ling
DL
Kong
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003713:Dendritic Cells / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D007167:Immunotherapy; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004337:Drug Carriers; D048271:Chitosan
Chitosan; Dendritic cell targeting; Immunotherapy; Nano-vaccine; Tumor cell lysates