DataVXACS NanoPaper
journal article·2023-07-11Open access

Direct In Vivo Activation of T Cells with Nanosized Immunofilaments Inhibits Tumor Growth and Metastasis

Lea Weiss, Jorieke Weiden, Yusuf Dölen, Emilia M. Grad, Eric A. W. van Dinther, Marjolein Schluck, Loek J. Eggermont, Guido van Mierlo, Uzi Gileadi, Ariadna Bartoló-Ibars, René Raavé, Mark A. J. Gorris, Lisa Maassen, Kiek Verrijp, Michael Valente, Bart Deplancke, Martijn Verdoes, Daniel Benitez-Ribas, Sandra Heskamp, Annemiek B. van Spriel, Carl G. Figdor, Roel Hammink

ACS Nano· Volume 17· Issue 13
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Source abstract

Abstract

Adoptive T cell therapy has successfully been implemented for the treatment of cancer. Nevertheless, ex vivo expansion of T cells by artificial antigen-presenting cells (aAPCs) remains cumbersome and can compromise T cell functionality, thereby limiting their therapeutic potential. We propose a radically different approach aimed at direct expansion of T cells in vivo, thereby omitting the need for large-scale ex vivo T cell production. We engineered nanosized immunofilaments (IFs), with a soluble semiflexible polyisocyanopeptide backbone that presents peptide-loaded major histocompatibility complexes and costimulatory molecules multivalently. IFs readily activated and expanded antigen-specific T cells like natural APCs, as evidenced by transcriptomic analyses of T cells. Upon intravenous injection, IFs reach the spleen and lymph nodes and induce antigen-specific T cell responses in vivo. Moreover, IFs display strong antitumor efficacy resulting in inhibition of the formation of melanoma metastases and reduction of primary tumor growth in synergy with immune checkpoint blockade. In conclusion, nanosized IFs represent a powerful modular platform for direct activation and expansion of antigen-specific T cells in vivo, which can greatly contribute to cancer immunotherapy.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: CAR-T cell therapy research · Immunotherapy and Immune Responses · Immune Cell Function and Interaction

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands

Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands

Institute for Chemical Immunology, 6525 GA Nijmegen, The Netherlands

Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 CH Lausanne, Switzerland

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom

Department of Immunology, Hospital Clinic, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Carrer Villarroel 170, 08036 Barcelona, Spain

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 HP Nijmegen, The Netherlands

Funding

H2020 LEIT Nanotechnologies · Oncode Institute · H2020 European Research Council · Nederlandse Organisatie voor Wetenschappelijk Onderzoek

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