Latex bead-based artificial antigen-presenting cells induce tumor-specific CTL responses in the native T-cell repertoires and inhibit tumor growth

Shen, Chuanlai; Cheng, Kai; Miao, Shenwei; Wang, Wei; He, Yong; Meng, Fanliang; Zhang, Jianqiong

doi:10.1016/j.imlet.2013.01.003

Cited by 27 publications

(18 citation statements)

References 28 publications

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“…Classical non-cellular aAPC feature two signals, an antigen-specific and a co-stimulatory signal. Most of the aAPC have been generated utilizing only one co-stimulatory signal but some groups successfully developed aAPC with combinations of those molecules such as anti-CD28/anti-LFA1(32) and anti-CD28/anti-4-1BB(33). However, to date no aAPC have been generated with more than the two classical signals.…”

Section: Discussionmentioning

confidence: 99%

CD47 EnhancesIn VivoFunctionality of Artificial Antigen-Presenting Cells

Bruns

Bessell

Varela

et al. 2015

Clinical Cancer Research

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Purpose Artificial Antigen-Presenting Cells, aAPC, have successfully been used to stimulate antigen-specific T cell responses in vitro as well as in vivo. While aAPC compare favorable to autologous dendritic cells in vitro, their effect in vivo might be diminished through rapid clearance by macrophages. Therefore, to prevent uptake and minimize clearance of aAPC by macrophages, and thereby increasing in vivo functionality, we investigated the efficiency of “don’t eat me” three-signal aAPC compared to classical two-signal aAPC. Experimental Design To generate “don’t eat me” aAPC, CD47 was additionally immobilized onto classical aAPC (aAPCCD47+). aAPC and aAPCCD47+ were analyzed in in vitro human primary T cell and macrophage co-cultures. In vivo efficiency was compared in a NOD/SCID T cell proliferation and a B16-SIY melanoma model. Results This study demonstrates that aAPCCD47+ in co-culture with human macrophages show a CD47 concentration dependent inhibition of phagocytosis, while their ability to generate and expand antigen-specific T cells was not affected. Furthermore, aAPCCD47+ generated T cells displayed equivalent killing abilities and polyfunctionality when compared to aAPC generated T cells. In addition, in vivo studies demonstrated an enhanced stimulatory capacity and tumor inhibition of aAPCCD47+ over normal aAPC in conjunction with diverging bio-distribution in different organs. Conclusion Our data for the first time show that aAPC functionalized with CD47 maintain their stimulatory capacity in vitro and demonstrate enhanced in vivo efficiency. Thus this next generation aAPCCD47+ have a unique potential to enhance the application of the aAPC technology for future immunotherapy approaches.

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Section: Discussionmentioning

confidence: 99%

CD47 EnhancesIn VivoFunctionality of Artificial Antigen-Presenting Cells

Bruns

Bessell

Varela

et al. 2015

Clinical Cancer Research

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“…aAPC can be functionalized with tumor-specific pMHC to activate a patient's immune system against cancer antigens and mediate tumor rejection [9–11]. They can be utilized in adoptive cell transfer (ACT) of ex vivo activated autologous T cells [9,12,13] or directly administered intravenously (IV) for in vivo anti-tumor T cell activation [14,15]. Synthetic aAPC platforms have distinct advantages over cellular systems in terms of long-term storage and the ability to optimize T cell activation and biocompatibility [16].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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“…However, no comprehensive examination between such constructs has been performed. Furthermore, multivalent MHC constructs can have other biophysical disadvantages: commonly used MHC tetramers have been coupled aAPC [144–146], but their rigid tetrahedral geometry orients a fraction of MHC molecules toward the particle surface and consequently away from the interacting T cell.…”

Section: Nanoscale Clustering and Nanoscale Aapcmentioning

confidence: 99%

“…In mice, iron-dextran micro-aAPC bearing dimeric MHC-peptide and anti-CD28 injected intravenously [15] can mediate regression of both subcutaneous melanoma and intravenous lung metastases. Similarly, latex particles administered both intravenously and subcutaneously generated robust antigen-specific T cell responses in mice, and subcutaneously administered microparticles mediated B16 melanoma rejection [146]. …”

Section: Applications Of Aapc: Past and Futurementioning

confidence: 99%