Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma

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• 作者：A.K. Kosmides^a ; ^b ; ^c ; ^e ; ¹ ; R.A. Meyer^a ; ^d ; ^e ; ¹ ; J.W. Hickey^a ; ^b ; ^c ; ^e ; K. Aje^b ; ^c ; K.N. Cheung^a ; ^d ; J.J. Green^a ; ^d ; ^e ; ^f ; ^g ; ^h ; ^{green@jhu.edu} ; J.P. Schneck^b ; ^c ; ^e ; ⁱ ; ^{jschnec1@jhmi.edu}
• 关键词：Artificial antigen presenting cell ; Immunotherapy ; CD8+ T-cell ; PD-1 ; Combination therapy
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：118
• 期：Complete
• 页码：16-26
• 全文大小：1716 K
• 卷排序：118

文摘

Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb). The combination of antigen-specific aAPC-based activation and anti-PD-1 mAb checkpoint blockade induced the greatest IFN-γ secretion by CD8+ T cells in vitro. Combination treatment also acted synergistically in an in vivo murine melanoma model to result in delayed tumor growth and extended survival, while either treatment alone had no effect. This was shown mechanistically to be due to decreased PD-1 expression and increased antigen-specific proliferation of CD8+ T cells within the tumor microenvironment and spleen. Thus, biomaterial-based therapy can synergize with other immunotherapies and motivates the translation of biomimetic combinatorial treatments.