Frontiers in Immunology (Dec 2021)
Single-Domain Antibodies for Targeting, Detection, and In Vivo Imaging of Human CD4+ Cells
- Bjoern Traenkle,
- Philipp D. Kaiser,
- Stefania Pezzana,
- Jennifer Richardson,
- Marius Gramlich,
- Teresa R. Wagner,
- Teresa R. Wagner,
- Dominik Seyfried,
- Dominik Seyfried,
- Melissa Weldle,
- Stefanie Holz,
- Yana Parfyonova,
- Stefan Nueske,
- Armin M. Scholz,
- Anne Zeck,
- Meike Jakobi,
- Nicole Schneiderhan-Marra,
- Martin Schaller,
- Andreas Maurer,
- Andreas Maurer,
- Cécile Gouttefangeas,
- Cécile Gouttefangeas,
- Cécile Gouttefangeas,
- Manfred Kneilling,
- Manfred Kneilling,
- Manfred Kneilling,
- Bernd J. Pichler,
- Bernd J. Pichler,
- Bernd J. Pichler,
- Dominik Sonanini,
- Dominik Sonanini,
- Ulrich Rothbauer,
- Ulrich Rothbauer,
- Ulrich Rothbauer
Affiliations
- Bjoern Traenkle
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Philipp D. Kaiser
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Stefania Pezzana
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Jennifer Richardson
- Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen, Germany
- Marius Gramlich
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Teresa R. Wagner
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Teresa R. Wagner
- Pharmaceutical Biotechnology, University of Tübingen, Tübingen, Germany
- Dominik Seyfried
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Dominik Seyfried
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Tübingen, Germany
- Melissa Weldle
- Pharmaceutical Biotechnology, University of Tübingen, Tübingen, Germany
- Stefanie Holz
- Pharmaceutical Biotechnology, University of Tübingen, Tübingen, Germany
- Yana Parfyonova
- Pharmaceutical Biotechnology, University of Tübingen, Tübingen, Germany
- Stefan Nueske
- Livestock Center of the Faculty of Veterinary Medicine, Ludwig Maximilians University Munich, Oberschleissheim, Germany
- Armin M. Scholz
- Livestock Center of the Faculty of Veterinary Medicine, Ludwig Maximilians University Munich, Oberschleissheim, Germany
- Anne Zeck
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Meike Jakobi
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Nicole Schneiderhan-Marra
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Martin Schaller
- Department of Dermatology, University of Tübingen, Tübingen, Germany
- Andreas Maurer
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Andreas Maurer
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies,” University of Tübingen, Tübingen, Germany
- Cécile Gouttefangeas
- Department of Immunology, Institute of Cell Biology, University of Tübingen, Tübingen, Germany
- Cécile Gouttefangeas
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Tübingen, Germany
- Cécile Gouttefangeas
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies,” University of Tübingen, Tübingen, Germany
- Manfred Kneilling
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Manfred Kneilling
- Department of Dermatology, University of Tübingen, Tübingen, Germany
- Manfred Kneilling
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies,” University of Tübingen, Tübingen, Germany
- Bernd J. Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Bernd J. Pichler
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Tübingen, Germany
- Bernd J. Pichler
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies,” University of Tübingen, Tübingen, Germany
- Dominik Sonanini
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany
- Dominik Sonanini
- Department of Medical Oncology and Pneumology, University of Tübingen, Tübingen, Germany
- Ulrich Rothbauer
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Ulrich Rothbauer
- Pharmaceutical Biotechnology, University of Tübingen, Tübingen, Germany
- Ulrich Rothbauer
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies,” University of Tübingen, Tübingen, Germany
- DOI
- https://doi.org/10.3389/fimmu.2021.799910
- Journal volume & issue
-
Vol. 12
Abstract
The advancement of new immunotherapies necessitates appropriate probes to monitor the presence and distribution of distinct immune cell populations. Considering the key role of CD4+ cells in regulating immunological processes, we generated novel single-domain antibodies [nanobodies (Nbs)] that specifically recognize human CD4. After in-depth analysis of their binding properties, recognized epitopes, and effects on T-cell proliferation, activation, and cytokine release, we selected CD4-specific Nbs that did not interfere with crucial T-cell processes in vitro and converted them into immune tracers for noninvasive molecular imaging. By optical imaging, we demonstrated the ability of a high-affinity CD4-Nb to specifically visualize CD4+ cells in vivo using a xenograft model. Furthermore, quantitative high-resolution immune positron emission tomography (immunoPET)/MR of a human CD4 knock-in mouse model showed rapid accumulation of 64Cu-radiolabeled CD4-Nb1 in CD4+ T cell-rich tissues. We propose that the CD4-Nbs presented here could serve as versatile probes for stratifying patients and monitoring individual immune responses during personalized immunotherapy in both cancer and inflammatory diseases.
Keywords
