Adjuvant-Loaded Subcellular Vesicles Derived From Disrupted Cancer Cells for Cancer Vaccination.
Adjuvant-Loaded Subcellular Vesicles Derived From Disrupted Cancer Cells for Cancer Vaccination.
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DOI：
10.1002/smll.201600061
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发表时间：
2016-05
期刊：
影响因子：
13.3
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
--
作者：
Cheung, Alexander S.;Koshy, Sandeep T.;Stafford, Alexander G.;Bastings, Maartje M. C.;Mooney, David J.
用于癌症免疫治疗的靶向亚单位疫苗不能捕获肿瘤抗原复杂性，而采用肿瘤裂解液的方法往往受到低效的抗原摄取和呈递以及低免疫原性的限制。在这里，整个癌细胞被加工成富含抗原的、膜封闭的亚细胞颗粒，称为“还原癌细胞”，反映了亲本癌细胞抗原库的多样性和广度，并且可以装载不同的佐剂有效载荷。这些囊泡颗粒增强了佐剂载荷的摄取，并增强了体外原代树突状细胞的激活。同样地，原代树突状细胞在体外比可溶性对应物或裂解物对照更有效地呈递减少的癌细胞相关抗原。在小鼠中，使用佐剂装载减少癌细胞的疫苗接种促进了抗原特异性细胞和体液免疫反应的诱导。综上所述，这些观察结果表明，佐剂负载的减少癌细胞可能在癌症疫苗中用作裂解物的替代品。整个癌细胞被加工成免疫原性亚细胞囊泡颗粒，可用于在体外和体内刺激抗原特异性免疫反应。这些颗粒保留了代表亲本细胞的广泛抗原库，并且可以装载不同的佐剂有效载荷。在各种癌症疫苗应用中，这些颗粒可能是一种优于裂解物的替代物，裂解物是一抗原制备的标准。
Targeted subunit vaccines for cancer immunotherapy do not capture tumor antigenic complexity, while approaches employing tumor lysate are often limited by inefficient antigen uptake and presentation, and low immunogenicity. Here, whole cancer cells were 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 could be loaded with disparate adjuvant payloads. These vesicular particles enhanced uptake of the adjuvant payload, and potentiated the activation of primary dendritic cells in vitro. Similarly, reduced cancer cell-associated antigens were more efficiently presented by primary dendritic cells in vitro than were soluble counterparts or lysate control. In mice, vaccination using adjuvant-loaded reduced cancer cells facilitated the induction of antigen-specific cellular and humoral immune responses. Taken together, these observations demonstrate that adjuvant-loaded reduced cancer cells could have utility in cancer vaccines as an alternative to lysate. Whole cancer cells were processed to generate immunogenic subcellular vesicular particles that can be used to stimulate antigen-specific immune responses in vitro and in vivo. The particles retain a broad antigen repertoire representative of the parent cells, and can be loaded with disparate adjuvant payloads. These particles may represent a superior alternative to lysate, the standard for primary antigen preparations, in various cancer vaccine applications.
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DOI：
10.1097/cji.0b013e3182811ae4
发表时间：
2013-02
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Prins RM;Wang X;Soto H;Young E;Lisiero DN;Fong B;Everson R;Yong WH;Lai A;Li G;Cloughesy TF;Liau LM
通讯作者：
Liau LM
影响因子：
38.3
作者：
通讯作者：
--
影响因子：
5.5
作者：
André, F;Scharz, NEC;Zitvogel, L
通讯作者：
Zitvogel, L
影响因子：
4.4
作者：
Li, M;Davey, GM;Heath, WR
通讯作者：
Heath, WR
影响因子：
46.9
作者：
Kim, Jaeyun;Li, Weiwei Aileen;Choi, Youngjin;Lewin, Sarah A.;Verbeke, Catia S.;Dranoff, Glenn;Mooney, David J.
通讯作者：
Mooney, David J.