Combination of a bispecific antibody and costimulatory antibody-ligand fusion proteins for targeted cancer immunotherapy

Journal of Immunotherapy
Nora HornigDafne Müller

Abstract

Initiation of a tumor-directed immune response and appropriate modulation of its progress are key issues in cancer immunotherapy. Combinatorial strategies addressing both aspects might therefore be especially suitable. Here, we report a targeted approach combining a bispecific antibody with 2 costimulatory antibody-ligand fusion proteins. According to the concept, the bispecific antibody (scDbFAP×CD3) retargets T cells in a MHC-independent manner to tumor cells, providing an artificial first signal that allows the costimulatory antibody-ligand fusion proteins (B7.2-Db and scFv-4-1BBL) likewise targeted to the tumor cells to modulate the T-cell response. In our model system, the target cells coexpress the fibroblast activation protein (FAP) and endoglin as antigens. ScDbFAPCD3 and B7.2-Db are targeted to FAP although by different antibody moieties, whereas scFv-4-1BBL is directed against endoglin. ScDbFAPCD3-induced T-cell stimulation could be enhanced by the addition of either B7.2-Db or scFv-4-1BBL and even further by the combination of both as shown in terms of cytokine release (interleukin-2/interferon γ), proliferation and activation marker expression (CD25). By combined costimulation, overall T-cell population strongly inc...Continue Reading

Citations

May 30, 2013·Cancer Immunology, Immunotherapy : CII·Nora HornigDafne Müller
Sep 11, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Dafne Müller
Dec 17, 2014·Journal of Translational Medicine·Katarzyna UrbanskaDaniel J Powell
Mar 11, 2016·Current Opinion in Immunology·Eugene A ZhukovskyMarcela V Maus
Jul 7, 2015·Pharmacology & Therapeutics·Dafne Müller
Oct 8, 2016·Cancer Immunology, Immunotherapy : CII·Peter EllmarkThomas H Tötterman
Oct 21, 2015·Nature Communications·Amarendra PeguGary J Nabel
Sep 20, 2018·Oncoimmunology·Sina Fellermeier-KopfRoland E Kontermann
Jul 1, 2020·Cancer Metastasis Reviews·Allison A Fitzgerald, Louis M Weiner
Jul 7, 2020·Frontiers in Immunology·Alba Rodriguez-GarciaSonia Guedan
Aug 20, 2017·Cancer Immunology Research·Mireya Paulina VelasquezStephen Gottschalk
Jul 25, 2021·Cancers·Ana Maia, Stefan Wiemann

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