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  Cytokine-Functionalized Synthetic Dendritic Cells for T Cell Targeted Immunotherapies

Eggermont, L. J., Hammink, R., Blank, K. G., Rowan, A. E., Tel, J., & Figdor, C. G. (2018). Cytokine-Functionalized Synthetic Dendritic Cells for T Cell Targeted Immunotherapies. Advanced Therapeutic, 1(6): 1800021. doi:10.1002/adtp.201800021.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-EDA6-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-C584-A
Genre: Journal Article

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 Creators:
Eggermont, Loek J., Author
Hammink, Roel, Author
Blank, Kerstin G.1, Author              
Rowan, Alan E., Author
Tel, Jurjen, Author
Figdor, Carl G., Author
Affiliations:
1Kerstin Blank, Mechano(bio)chemie, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_2301698              

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Free keywords: artificial antigen-presenting cells, cytokines, immunotherapy, polyisocyanopeptides, synthetic dendritic cell
 Abstract: Widespread application of cytokine-based therapies is hampered by severe toxic side effects, resulting from off-target (immune) cell stimulation. This emphasizes the need for more precise targeting of cytokines to immune cells. While cytokines are generally active as soluble proteins, it is demonstrated here that synthetic mimics of immune cells based on polyisocyanopeptides (PICs), called synthetic dendritic cells (sDCs) can efficiently present immobilized cytokines to T cells, when targeted by anti-CD3 antibodies. Anti-CD3/IL-2-functionalized PICs induce strong T cell activation and proliferation, when compared to PICs functionalized with interleukin-2 (IL-2) alone. In contrast to the semi-flexible PICs, immobilization of IL-2 on a rigid micro-sized scaffold results in significant loss of IL-2 activity, signifying the importance of molecular flexibility on the PIC polymers to maintain function. Similarly, anti-CD3/IFNα-functionalized PICs support long-term proliferation of T cells. Interferon-α containing sDCs additionally promote the development of cytotoxic effector functions of T cells with limited upregulation of the inhibitory immune checkpoint PD-1. This high cytolytic activity and low PD-1 expression are essential to maintain effective anti-cancer activity. Together, these results demonstrate that PICs form unique nano-sized scaffolds that efficiently present immobilized cytokines to T cells, thus creating a powerful tool to improve cytokine-based immunotherapies without concomitant off-target toxicity.

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Language(s): eng - English
 Dates: 2018-08-052018
 Publication Status: Published in print
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 Identifiers: DOI: 10.1002/adtp.201800021
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Title: Advanced Therapeutic
  Alternative Title : Adv. Therap.
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: - Volume / Issue: 1 (6) Sequence Number: 1800021 Start / End Page: - Identifier: ISSN: 2366-3987