Adjuvant-Loaded Subcellular Vesicles Derived From Disrupted Cancer Cells for Cancer Vaccination

被引:35
作者
Cheung, Alexander S. [1 ,2 ]
Koshy, Sandeep T. [1 ,2 ,3 ]
Stafford, Alexander G. [2 ]
Bastings, Maartje M. C. [2 ,4 ,5 ]
Mooney, David J. [1 ,2 ]
机构
[1] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[2] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[3] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[4] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[5] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA
基金
美国国家科学基金会;
关键词
ANTITUMOR IMMUNITY; DENDRITIC CELLS; ANTIGEN; DELIVERY; VACCINES; NANOPARTICLES; CONJUGATION; ACTIVATION; INDUCTION; PROTEIN;
D O I
10.1002/smll.201600061
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Targeted subunit vaccines for cancer immunotherapy do not capture tumor antigenic complexity, and approaches employing tumor lysate are often limited by inefficient antigen uptake and presentation, and low immunogenicity. Here, whole cancer cells are processed to generate antigen-rich, membrane-enclosed subcellular particles, termed "reduced cancer cells", that reflect the diversity and breadth of the parent cancer cell antigen repertoire, and can be loaded with disparate adjuvant payloads. These vesicular particles enhance the uptake of the adjuvant payload, and potentiate the activation of primary dendritic cells in vitro. Similarly, reduced cancer cell-associated antigens are more efficiently presented by primary dendritic cells in vitro than their soluble counterparts or lysate control. In mice, vaccination using adjuvant-loaded reduced cancer cells facilitates the induction of antigen-specific cellular and humoral immune responses. Taken together, these observations demonstrate that adjuvant-loaded reduced cancer cells could be utilized in cancer vaccines as an alternative to lysate.
引用
收藏
页码:2321 / 2333
页数:13
相关论文
共 43 条
[1]   Identification of Immune Factors Regulating Antitumor Immunity Using Polymeric Vaccines with Multiple Adjuvants [J].
Ali, Omar A. ;
Verbeke, Catia ;
Johnson, Chris ;
Sands, R. Warren ;
Lewin, Sarah A. ;
White, Des ;
Doherty, Edward ;
Dranoff, Glenn ;
Mooney, David J. .
CANCER RESEARCH, 2014, 74 (06) :1670-1681
[2]   Inflammatory Cytokines Presented from Polymer Matrices Differentially Generate and Activate DCs In Situ [J].
Ali, Omar A. ;
Tayalia, Prakriti ;
Shvartsman, Dmitry ;
Lewin, Sarah ;
Mooney, David J. .
ADVANCED FUNCTIONAL MATERIALS, 2013, 23 (36) :4621-4628
[3]  
Ali OA, 2009, SCI TRANSL MED, V1, DOI 10.1126/scitranslmed.3000359
[4]  
Ali OA, 2009, NAT MATER, V8, P151, DOI [10.1038/NMAT2357, 10.1038/nmat2357]
[5]   Tumor-derived exosomes:: a new source of tumor rejection antigens [J].
André, F ;
Scharz, NEC ;
Chaput, N ;
Flament, C ;
Raposo, G ;
Amigorena, S ;
Angevin, E ;
Zitvogel, L .
VACCINE, 2002, 20 :A28-A31
[6]  
Black M, 2010, EXPERT REV VACCINES, V9, P157, DOI [10.1586/erv.09.160, 10.1586/ERV.09.160]
[7]   Toll-dependent selection of microbial antigens for presentation by dendritic cells [J].
Blander, JM ;
Medzhitov, R .
NATURE, 2006, 440 (7085) :808-812
[8]   Vesicle size influences the trafficking, processing, and presentation of antigens in lipid vesicles [J].
Brewer, JM ;
Pollock, KGJ ;
Tetley, L ;
Russell, DG .
JOURNAL OF IMMUNOLOGY, 2004, 173 (10) :6143-6150
[9]   Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation [J].
Burgdorf, Sven ;
Schoelz, Christian ;
Kautz, Andreas ;
Tampe, Robert ;
Kurts, Christian .
NATURE IMMUNOLOGY, 2008, 9 (05) :558-566
[10]   Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose [J].
de Titta, Alexandre ;
Ballester, Marie ;
Julier, Ziad ;
Nembrini, Chiara ;
Jeanbart, Laura ;
van der Vlies, Andre J. ;
Swartz, Melody A. ;
Hubbell, Jeffrey A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (49) :19902-19907