The construction of a lymphoma cell-based, DC-targeted vaccine, and its application in lymphoma prevention and cure

被引:14
作者
Zhou, Tianlin [1 ,2 ]
Peng, Jinrong [1 ,2 ]
Hao, Ying [1 ,2 ]
Shi, Kun [1 ,2 ]
Zhou, Kai [1 ,2 ]
Yang, Yun [1 ,2 ]
Yang, Chengli [1 ,2 ]
He, Xinlong [1 ,2 ]
Chen, Xinmian [3 ]
Qian, Zhiyong [1 ,2 ]
机构
[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr, Chengdu 610041, Peoples R China
[2] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China
[3] Univ Elect Sci & Technol China, Sch Med, Personalised Drug Therapy Key Lab Sichuan Prov, Dept Pharm,Sichuan Prov Peoples Hosp, Chengdu 610072, Peoples R China
基金
中国国家自然科学基金;
关键词
Non-hodgkin lymphoma; DCs targeting; Man-EG7/CH@CpG vaccine; Combinational therapy; DRUG-DELIVERY; CANCER-IMMUNOTHERAPY; DENDRITIC CELLS; TUMOR; NANOPARTICLES; CHEMOTHERAPY; COMBINATION; ANTIGENS; PEPTIDE; DEATH;
D O I
10.1016/j.bioactmat.2020.09.002
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
In recent years, Non-Hodgkin lymphoma (NHL) has been one of the most fast-growing malignant tumor diseases. NHL poses severe damages to physical health and a heavy burden to patients. Traditional therapies (chemotherapy or radiotherapy) bring some benefit to patients, but have severe adverse effects and do not prevent relapse. The relevance of emerging immunotherapy options (immune-checkpoint blockers or adoptive cellular methods) for NHL remains uncertain, and more intensive evaluations are needed. In this work, inspired by the idea of vaccination to promote an immune response to destroy tumors, we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties. In this vaccine, natural tumor cells are used as a vector to load CpG-ODN, and following lethal irradiation, the formulations were decorated with mannose. The study of the characterization of the double-improved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence, which displayed an antitumor function. In the lymphoma prevention model, the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency. Furthermore, unlike the non-improved vaccine, the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model. Next, to improve the moderate therapeutic effect of the mono-treatment method, we incorporated a chemotherapeutic drug (doxorubicin, DOX) into the process of vaccination and devised a combination regimen. Fortunately, a tumor inhibition rate of similar to 85% was achieved via the combination therapy, which could not be achieved by mono-chemotherapy or mono-immunotherapy. In summary, the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.
引用
收藏
页码:697 / 711
页数:15
相关论文
共 90 条
[1]   Surface engineering tumor cells with adjuvant-loaded particles for use as cancer vaccines [J].
Ahmed, Kawther K. ;
Geary, Sean M. ;
Salem, Aliasger K. .
JOURNAL OF CONTROLLED RELEASE, 2017, 248 :1-9
[2]   Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation [J].
Anderson, Ana C. ;
Joller, Nicole ;
Kuchroo, Vijay K. .
IMMUNITY, 2016, 44 (05) :989-1004
[3]   PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma [J].
Ansell, Stephen M. ;
Lesokhin, Alexander M. ;
Borrello, Ivan ;
Halwani, Ahmad ;
Scott, Emma C. ;
Gutierrez, Martin ;
Schuster, Stephen J. ;
Millenson, Michael M. ;
Cattry, Deepika ;
Freeman, Gordon J. ;
Rodig, Scott J. ;
Chapuy, Bjoern ;
Ligon, Azra H. ;
Zhu, Lili ;
Grosso, Joseph F. ;
Kim, Su Young ;
Timmerman, John M. ;
Shipp, Margaret A. ;
Armand, Philippe .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :311-319
[4]   Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy [J].
Areti, Aparna ;
Yerra, Veera Ganesh ;
Naidu, V. G. M. ;
Kumar, Ashutosh .
REDOX BIOLOGY, 2014, 2 :289-295
[5]   Non-Hodgkin lymphoma [J].
Armitage, James O. ;
Gascoyne, Randy D. ;
Lunning, Matthew A. ;
Cavalli, Franco .
LANCET, 2017, 390 (10091) :298-310
[6]   Expression of a mannose/fucose membrane lectin on human dendritic cells [J].
Avrameas, A ;
McIlroy, D ;
Hosmalin, A ;
Autran, B ;
Debre, P ;
Monsigny, M ;
Roche, AC ;
Midoux, P .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (02) :394-400
[7]   Cross-priming for antitumor CTL induced by soluble Ag plus polyI:C depends on the TICAM-1 pathway in mouse CD11c+/CD8α+ dendritic cells [J].
Azuma, Masahiro ;
Ebihara, Takashi ;
Oshiumi, Hiroyuki ;
Matsumoto, Misako ;
Seya, Tsukasa .
ONCOIMMUNOLOGY, 2012, 1 (05) :581-592
[8]   The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence [J].
Barker, Holly E. ;
Paget, James T. E. ;
Khan, Aadil A. ;
Harrington, Kevin J. .
NATURE REVIEWS CANCER, 2015, 15 (07) :409-425
[9]   CD169+ macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes [J].
Barral, Patricia ;
Polzella, Paolo ;
Bruckbauer, Andreas ;
van Rooijen, Nico ;
Besra, Gurdyal S. ;
Cerundolo, Vincenzo ;
Batista, Facundo D. .
NATURE IMMUNOLOGY, 2010, 11 (04) :303-U48
[10]   Chitosan-based drug delivery systems [J].
Bernkop-Schnuerch, Andreas ;
Duennhaupt, Sarah .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2012, 81 (03) :463-469