Therapeutic nanoworms: Towards novel synthetic dendritic cells for immunotherapy

Subhra Mandal; Z.H. Eksteen-Akeroyd; M.J. Jacobs; Roel Hammink; M. Koepf; A.J.A. Lambeck; J.C.M. Hest, van; C.J. Wilson; K. Blank; C.G. Figdor; A.E. Rowan

doi:10.1039/c3sc51399h

Therapeutic nanoworms: Towards novel synthetic dendritic cells for immunotherapy

Subhra Mandal, Z.H. Eksteen-Akeroyd, M.J. Jacobs, Roel Hammink, M. Koepf, A.J.A. Lambeck, J.C.M. Hest, van, C.J. Wilson, K. Blank, C.G. Figdor, A.E. Rowan

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Abstract

A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5-10 nm, length ∼200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.

Original language	English
Pages (from-to)	4168-4174
Number of pages	7
Journal	Chemical Science
Volume	4
Issue number	11
DOIs	https://doi.org/10.1039/c3sc51399h
Publication status	Published - 2013
Externally published	Yes

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title = "Therapeutic nanoworms: Towards novel synthetic dendritic cells for immunotherapy",

abstract = "A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5-10 nm, length ∼200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.",

author = "Subhra Mandal and Z.H. Eksteen-Akeroyd and M.J. Jacobs and Roel Hammink and M. Koepf and A.J.A. Lambeck and {Hest, van}, J.C.M. and C.J. Wilson and K. Blank and C.G. Figdor and A.E. Rowan",

year = "2013",

doi = "10.1039/c3sc51399h",

language = "English",

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AU - Mandal, Subhra

AU - Eksteen-Akeroyd, Z.H.

AU - Jacobs, M.J.

AU - Hammink, Roel

AU - Koepf, M.

AU - Lambeck, A.J.A.

AU - Hest, van, J.C.M.

AU - Wilson, C.J.

AU - Blank, K.

AU - Figdor, C.G.

AU - Rowan, A.E.

PY - 2013

Y1 - 2013

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AB - A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5-10 nm, length ∼200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.

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JF - Chemical Science

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Therapeutic nanoworms: Towards novel synthetic dendritic cells for immunotherapy

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