Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens
| Autor: | Nicholas S. Wilson, Sylvia Dietrich, Randi Gombos, Ana M. Martín González, Robert Stein, Lukasz Swiech, David Savitsky, Ben A. Croker, Benjamin Morin, Jennifer Buell, Mariana Manrique, Antoine Tanne, Jeremy D. Waight, Christine Brittsan, Dhan Chand, Belinda Akpeng, Thomas Horn |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Antigens Differentiation T-Lymphocyte Cancer Research medicine.drug_class T cell medicine.medical_treatment T-Lymphocytes Receptors Antigen T-Cell Antigen-Presenting Cells Monoclonal antibody Article Immunological synapse 03 medical and health sciences 0302 clinical medicine TIGIT Cancer immunotherapy Antigen Neoplasms medicine Animals Humans CTLA-4 Antigen Receptors Immunologic Mice Inbred BALB C Chemistry Receptors IgG Antibodies Monoclonal Fragment crystallizable region Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Receptor clustering Protein Binding Signal Transduction |
| Zdroj: | Cancer cell. 33(6) |
| ISSN: | 1878-3686 |
| Popis: | Summary The co-engagement of fragment crystallizable (Fc) gamma receptors (FcγRs) with the Fc region of recombinant immunoglobulin monoclonal antibodies (mAbs) and its contribution to therapeutic activity has been extensively studied. For example, Fc-FcγR interactions have been shown to be important for mAb-directed effector cell activities, as well as mAb-dependent forward signaling into target cells via receptor clustering. Here we identify a function of mAbs targeting T cell-expressed antigens that involves FcγR co-engagement on antigen-presenting cells (APCs). In the case of mAbs targeting CTLA-4 and TIGIT, the interaction with FcγR on APCs enhanced antigen-specific T cell responses and tumoricidal activity. This mechanism extended to an anti-CD45RB mAb, which led to FcγR-dependent regulatory T cell expansion in mice. |
| Databáze: | OpenAIRE |
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