Spherical Nucleic Acid Vaccine Structure Markedly Influences Adaptive Immune Responses of Clinically Utilized Prostate Cancer Targets.
Spherical Nucleic Acid Vaccine Structure Markedly Influences Adaptive Immune Responses of Clinically Utilized Prostate Cancer Targets.
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球形核酸疫苗结构显着影响临床使用的前列腺癌靶标的适应性免疫反应。
DOI：
10.1002/adhm.202101262
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发表时间：
2021-11
影响因子：
10
通讯作者：
Mirkin CA
中科院分区：
文献类型：
--
作者：
Teplensky MH;Dittmar JW;Qin L;Wang S;Evangelopoulos M;Zhang B;Mirkin CA
Cancer vaccines, which activate the immune system against a target antigen, are attractive for prostate cancer, where multiple upregulated protein targets are identified. However, many clinical trials implementing peptides targeting these proteins have yielded suboptimal results. Using spherical nucleic acids (SNAs), we explore how precise architectural control of vaccine components can activate a robust antigen-specific immune response in comparison to clinical formulations of the same targets. The SNA vaccines incorporate peptides for human prostate-specific membrane antigen (PSMA) or T-cell receptor γ alternate reading frame protein (TARP) into an optimized architecture, resulting in high rates of immune activation and cytolytic ability in humanized mice and human peripheral blood mononuclear cells (hPBMCs). Specifically, administered SNAs elevate the production and secretion of cytokines and increase polyfunctional cytotoxic T cells and effector memory. Importantly, T cells raised from immunized mice potently kill targets, including clinically-relevant cells expressing the whole PSMA protein. Treatment of hPBMCs increases co-stimulatory markers and cytolytically active T cells. This work demonstrates the importance of vaccine structure and its ability to reformulate and elevate clinical targets. Moreover, it encourages the field to reinvestigate ineffective peptide targets and repackage them into optimally structured vaccines to harness antigen potency and enhance clinical outcomes. Using modular spherical nucleic acids (SNAs), we show how vaccine architecture dramatically impacts immune responses (i.e., cytolytic T cell priming) when incorporating clinical peptide targets against prostate cancer. By considering structure in vaccine design, we present a way one can reformulate failed clinical targets and enhance their potency.
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DOI：
10.1200/edbk_278853
发表时间：
2020-03-01
期刊：
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
影响因子：
--
作者：
de Almeida, Daniel Vargas P;Fong, Lawrence;Autio, Karen A
通讯作者：
Autio, Karen A
DOI：
10.1073/pnas.2005794117
发表时间：
2020-07-28
影响因子：
11.1
作者：
Callmann, Cassandra E.;Cole, Lisa E.;Mirkin, Chad A.
通讯作者：
Mirkin, Chad A.
DOI：
10.1007/s00262-017-2084-x
发表时间：
2018-12
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Berzofsky JA;Terabe M;Trepel JB;Pastan I;Stroncek DF;Morris JC;Wood LV
通讯作者：
Wood LV
影响因子：
7.2
作者：
De Groot, Rosa;Van Loenen, Marleen M.;Wolkers, Monika C.
通讯作者：
Wolkers, Monika C.
DOI：
10.1073/pnas.1305804110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Choi, Chung Hang J.;Hao, Liangliang;Mirkin, Chad A.
通讯作者：
Mirkin, Chad A.