Nanoengineering Approaches to The Design of Artificial Antigen-Presenting Cells

Sunshine, Joel C.; Green, Jordan J.

doi:10.2217/nnm.13.98

Cited by 78 publications

(67 citation statements)

References 103 publications

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“…While these studies prove in vitro and in vivo functionality of our aAPC, in vivo delivery and biodistribution is mainly determined by the size of the aAPC scaffold(10,12,20). Micro-meter sized aAPC display limited lymphatic drainage(21) and are cleared and phagocytosed by professional phagocytes such as macrophages and immature DC(22–24).…”

Section: Introductionmentioning

confidence: 76%

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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: Introductionmentioning

confidence: 76%

“…Many groups have developed non-cellular aAPC with in vivo applicability to establish a cost-, labour- and time-saving technology(20,30,31). Classical non-cellular aAPC feature two signals, an antigen-specific and a co-stimulatory signal.…”

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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“…[88] Interestingly, nanoparticle based artificial APCs have also been developed to mimic the APC-T cell interaction and to induce the CTL responses. [89] In this direction, as an artificial APC, sub 100 nm sized iron oxide nanoparticles coated with dextran and conjugated with stimulatory molecules have shown to induce the T-cell receptor clustering under magnetic field and activate näive T cells. [90] More details on various nanoparticles strategies developed for cancer immunotherapy have been extensively reviewed elsewhere.…”

Section: Next Generation Nanomedicinesmentioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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“…Thus, while existing aAPC fabrication techniques generally rely on randomly distributed ligands, these findings suggest it may be possible to fine-tune T cell activation from aAPC by patterning activating ligands in ways that mimic T cell-APC interaction. However, this will require the development of technologies for heterogeneous ligand distribution on particle surfaces [108,109] (Figure 3A). …”

Section: Microscale T Cell-aapc Interactionsmentioning

confidence: 99%

“…Further application of heterogeneous MHC clustering on aAPC will require the development of biocompatible, readily synthesized platforms with spatially controlled receptor patterning [109]. For example, the Little group recently reported a technique based on interfacial condensation of a liquid mask to create microspheres with “patchy” protein islets [156].…”

Section: Nanoscale Clustering and Nanoscale Aapcmentioning

confidence: 99%