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396 results on '"Gouttefangeas, Cécile"'

5. Automated Analysis of Flow Cytometry Data to Reduce Inter-Lab Variation in the Detection of Major Histocompatibility Complex Multimer-Binding T Cells

Author

Pedersen, Natasja Wulff, Chandran, P Anoop, Qian, Yu, Rebhahn, Jonathan, Petersen, Nadia Viborg, Hoff, Mathilde Dalsgaard, White, Scott, Lee, Alexandra J, Stanton, Rick, Halgreen, Charlotte, Jakobsen, Kivin, Mosmann, Tim, Gouttefangeas, Cécile, Chan, Cliburn, Scheuermann, Richard H, and Hadrup, Sine Reker

Subjects
Biomedical and Clinical Sciences, Immunology, Bioengineering, major histocompatibility complex multimers, antigen-specific T cells, automated gating, computational analysis, major histocompatibility complex dextramers, flow cytometry, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract

Manual analysis of flow cytometry data and subjective gate-border decisions taken by individuals continue to be a source of variation in the assessment of antigen-specific T cells when comparing data across laboratories, and also over time in individual labs. Therefore, strategies to provide automated analysis of major histocompatibility complex (MHC) multimer-binding T cells represent an attractive solution to decrease subjectivity and technical variation. The challenge of using an automated analysis approach is that MHC multimer-binding T cell populations are often rare and therefore difficult to detect. We used a highly heterogeneous dataset from a recent MHC multimer proficiency panel to assess if MHC multimer-binding CD8+ T cells could be analyzed with computational solutions currently available, and if such analyses would reduce the technical variation across different laboratories. We used three different methods, FLOw Clustering without K (FLOCK), Scalable Weighted Iterative Flow-clustering Technique (SWIFT), and ReFlow to analyze flow cytometry data files from 28 laboratories. Each laboratory screened for antigen-responsive T cell populations with frequency ranging from 0.01 to 1.5% of lymphocytes within samples from two donors. Experience from this analysis shows that all three programs can be used for the identification of high to intermediate frequency of MHC multimer-binding T cell populations, with results very similar to that of manual gating. For the less frequent populations (

Published
2017

6. SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition

Author

Nelde, Annika, Bilich, Tatjana, Heitmann, Jonas S., Maringer, Yacine, Salih, Helmut R., Roerden, Malte, Lübke, Maren, Bauer, Jens, Rieth, Jonas, Wacker, Marcel, Peter, Andreas, Hörber, Sebastian, Traenkle, Bjoern, Kaiser, Philipp D., Rothbauer, Ulrich, Becker, Matthias, Junker, Daniel, Krause, Gérard, Strengert, Monika, Schneiderhan-Marra, Nicole, Templin, Markus F., Joos, Thomas O., Kowalewski, Daniel J., Stos-Zweifel, Vlatka, Fehr, Michael, Rabsteyn, Armin, Mirakaj, Valbona, Karbach, Julia, Jäger, Elke, Graf, Michael, Gruber, Lena-Christin, Rachfalski, David, Preuß, Beate, Hagelstein, Ilona, Märklin, Melanie, Bakchoul, Tamam, Gouttefangeas, Cécile, Kohlbacher, Oliver, Klein, Reinhild, Stevanović, Stefan, Rammensee, Hans-Georg, and Walz, Juliane S.

Published
2021
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8. 638 Characterisation of the immune response to EO2401, a new immunotherapy approach against cancer, plus nivolumab in recurrent glioblastoma: The EOGBM1–18/ROSALIE study

Author

Maia, Ana, primary, Toussaint, Hélène, additional, Magalhaes, Joao Gamelas, additional, Idbaih, Ahmed, additional, Villar, Maria Vieito, additional, Tabatabai, Ghazaleh, additional, Stradella, Agostina, additional, Ghiringhelli, Francois, additional, Burger, Michael C, additional, Mildenberger, Iris, additional, Herrlinger, Ulrich, additional, González, Macarena, additional, Hervieu, Alice, additional, GilMartin, Marta, additional, Renovanz, Mirjam, additional, Touat, Mehdi, additional, Wen, Patrick, additional, Wick, Antje, additional, Bonny, Christophe, additional, Paillarse, Jean-Michel, additional, Reardon, David, additional, Wick, Wolfgang, additional, and Gouttefangeas, Cécile, additional

Published
2023
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9. CTIM-25. EO2401 PEPTIDE IMMUNOTHERAPY + NIVOLUMAB +/- BEVACIZUMAB IN FIRST RECURRENT GLIOBLASTOMA: THE PHASE 1/2 EOGBM1-18/ROSALIE STUDY (NCT04116658)

Author

Reardon, David, primary, Idbaih, Ahmed, additional, Vieito, Maria, additional, Ghiringhelli, François, additional, Stradella, Agostina, additional, Tabatabai, Ghazaleh, additional, Burger, Michael C, additional, Mildenberger, Iris, additional, Herrlinger, Ulrich, additional, Wen, Patrick, additional, Touat, Mehdi, additional, Wick, Antje, additional, González, Macarena, additional, Hervieu, Alice, additional, GilMartin, Marta, additional, Renovanz, Mirjam, additional, Gouttefangeas, Cécile, additional, Maia, Ana, additional, Bonny, Christophe, additional, Paillarse, Jean-Michel, additional, Chêne, Laurent, additional, Fagerberg, Jan, additional, and Wick, Wolfgang, additional

Published
2023
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14. Actively personalized vaccination trial for newly diagnosed glioblastoma

Author

Hilf, Norbert, Kuttruff-Coqui, Sabrina, Frenzel, Katrin, Bukur, Valesca, Stevanovic, Stefan, Gouttefangeas, Cécile, and Platten, Michael

Subjects
Precision medicine -- Methods, CD8 lymphocytes -- Analysis, Vaccines -- Dosage and administration -- Testing, Vaccination -- Dosage and administration, CD4 lymphocytes -- Analysis, Glioblastomas -- Diagnosis -- Drug therapy, Environmental issues, Science and technology, Zoology and wildlife conservation, APVAC2 (Vaccine) -- Dosage and administration -- Testing, APVAC1 (Vaccine) -- Dosage and administration -- Testing
Abstract

Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors.sup.1,2. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential.sup.3. There is limited intratumoural infiltration of immune cells.sup.4 in glioblastoma and these tumours contain only 30-50 non-synonymous mutations.sup.5. Exploitation of the full repertoire of tumour antigens--that is, both unmutated antigens and neoepitopes--may offer more effective immunotherapies, especially for tumours with a low mutational load. Here, in the phase I trial GAPVAC-101 of the Glioma Actively Personalized Vaccine Consortium (GAPVAC), we integrated highly individualized vaccinations with both types of tumour antigens into standard care to optimally exploit the limited target space for patients with newly diagnosed glioblastoma. Fifteen patients with glioblastomas positive for human leukocyte antigen (HLA)-A*02:01 or HLA-A*24:02 were treated with a vaccine (APVAC1) derived from a premanufactured library of unmutated antigens followed by treatment with APVAC2, which preferentially targeted neoepitopes. Personalization was based on mutations and analyses of the transcriptomes and immunopeptidomes of the individual tumours. The GAPVAC approach was feasible and vaccines that had poly-ICLC (polyriboinosinic-polyribocytidylic acid-poly-l-lysine carboxymethylcellulose) and granulocyte-macrophage colony-stimulating factor as adjuvants displayed favourable safety and strong immunogenicity. Unmutated APVAC1 antigens elicited sustained responses of central memory CD8.sup.+ T cells. APVAC2 induced predominantly CD4.sup.+ T cell responses of T helper 1 type against predicted neoepitopes. In a phase I trial, highly individualized peptide vaccines against unmutated tumour antigens and neoepitopes elicited sustained responses in CD8.sup.+ and CD4.sup.+ T cells, respectively, in patients with newly diagnosed glioblastoma., Author(s): Norbert Hilf [sup.1] , Sabrina Kuttruff-Coqui [sup.1] , Katrin Frenzel [sup.2] , Valesca Bukur [sup.2] , Stefan Stevanovic [sup.3] [sup.4] , Cécile Gouttefangeas [sup.3] [sup.4] [sup.5] , Michael Platten [...]

Published
2019
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16. Defining the Critical Hurdles in Cancer Immunotherapy

Author

Fox, Bernard A, Schendel, Dolores J, Butterfield, Lisa H, Aamdal, Steinar, Allison, James P, Ascierto, Paolo, Atkins, Michael B, Bartunkova, Jirina, Bergmann, Lothar, Berinstein, Neil, Bonorino, Cristina C, Borden, Ernest, Bramson, Jonathan L, Britten, Cedrik M, Cao, Xuetao, Carson, William E, Chang, Alfred E, Characiejus, Dainius, Choudhury, A Raja, Coukos, George, de Gruijl, Tanja, Dillman, Robert O, Dolstra, Harry, Dranoff, Glenn, Durrant, Lindy G, Finke, James H, Galon, Jerome, Gollob, Jared A, Gouttefangeas, Cécile, Grizzi, Fabio, Guida, Michele, Håkansson, Leif, Hege, Kristen, Herberman, Ronald B, Hodi, F Stephen, Hoos, Axel, Huber, Christoph, Hwu, Patrick, Imai, Kohzoh, Jaffee, Elizabeth M, Janetzki, Sylvia, June, Carl H, Kalinski, Pawel, Kaufman, Howard L, Kawakami, Koji, Kawakami, Yutaka, Keilholtz, Ulrich, Khleif, Samir N, Kiessling, Rolf, Kotlan, Beatrix, Kroemer, Guido, Lapointe, Rejean, Levitsky, Hyam I, Lotze, Michael T, Maccalli, Cristina, Maio, Michele, Marschner, Jens-Peter, Mastrangelo, Michael J, Masucci, Giuseppe, Melero, Ignacio, Melief, Cornelius, Murphy, William J, Nelson, Brad, Nicolini, Andrea, Nishimura, Michael I, Odunsi, Kunle, Ohashi, Pamela S, O'Donnell-Tormey, Jill, Old, Lloyd J, Ottensmeier, Christian, Papamichail, Michael, Parmiani, Giorgio, Pawelec, Graham, Proietti, Enrico, Qin, Shukui, Rees, Robert, Ribas, Antoni, Ridolfi, Ruggero, Ritter, Gerd, Rivoltini, Licia, Romero, Pedro J, Salem, Mohamed L, Scheper, Rik J, Seliger, Barbara, Sharma, Padmanee, Shiku, Hiroshi, Singh-Jasuja, Harpreet, Song, Wenru, Straten, Per, Tahara, Hideaki, Tian, Zhigang, van Der Burg, Sjoerd H, von Hoegen, Paul, Wang, Ena, Welters, Marij JP, Winter, Hauke, Withington, Tara, Wolchok, Jedd D, Xiao, Weihua, and Zitvogel, Laurence

Abstract

Abstract Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

Published
2011

20. Supplementary Table 1 from Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Author

Laske, Karoline, primary, Shebzukhov, Yuriy V., primary, Grosse-Hovest, Ludger, primary, Kuprash, Dmitry V., primary, Khlgatian, Svetlana V., primary, Koroleva, Ekaterina P., primary, Sazykin, Alexey Y., primary, Penkov, Dmitry N., primary, Belousov, Pavel V., primary, Stevanović, Stefan, primary, Vass, Verona, primary, Walter, Steffen, primary, Eisel, David, primary, Schmid-Horch, Barbara D., primary, Nedospasov, Sergei A., primary, Rammensee, Hans-Georg, primary, and Gouttefangeas, Cécile, primary

Published
2023
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21. Supplementary Table 3 from Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Author

Laske, Karoline, primary, Shebzukhov, Yuriy V., primary, Grosse-Hovest, Ludger, primary, Kuprash, Dmitry V., primary, Khlgatian, Svetlana V., primary, Koroleva, Ekaterina P., primary, Sazykin, Alexey Y., primary, Penkov, Dmitry N., primary, Belousov, Pavel V., primary, Stevanović, Stefan, primary, Vass, Verona, primary, Walter, Steffen, primary, Eisel, David, primary, Schmid-Horch, Barbara D., primary, Nedospasov, Sergei A., primary, Rammensee, Hans-Georg, primary, and Gouttefangeas, Cécile, primary

Published
2023
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22. Supplementary Figure 1 from Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Author

Laske, Karoline, primary, Shebzukhov, Yuriy V., primary, Grosse-Hovest, Ludger, primary, Kuprash, Dmitry V., primary, Khlgatian, Svetlana V., primary, Koroleva, Ekaterina P., primary, Sazykin, Alexey Y., primary, Penkov, Dmitry N., primary, Belousov, Pavel V., primary, Stevanović, Stefan, primary, Vass, Verona, primary, Walter, Steffen, primary, Eisel, David, primary, Schmid-Horch, Barbara D., primary, Nedospasov, Sergei A., primary, Rammensee, Hans-Georg, primary, and Gouttefangeas, Cécile, primary

Published
2023
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23. Data from Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Author

Laske, Karoline, primary, Shebzukhov, Yuriy V., primary, Grosse-Hovest, Ludger, primary, Kuprash, Dmitry V., primary, Khlgatian, Svetlana V., primary, Koroleva, Ekaterina P., primary, Sazykin, Alexey Y., primary, Penkov, Dmitry N., primary, Belousov, Pavel V., primary, Stevanović, Stefan, primary, Vass, Verona, primary, Walter, Steffen, primary, Eisel, David, primary, Schmid-Horch, Barbara D., primary, Nedospasov, Sergei A., primary, Rammensee, Hans-Georg, primary, and Gouttefangeas, Cécile, primary

Published
2023
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24. Supplementary Figure Legends from Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Author

Laske, Karoline, primary, Shebzukhov, Yuriy V., primary, Grosse-Hovest, Ludger, primary, Kuprash, Dmitry V., primary, Khlgatian, Svetlana V., primary, Koroleva, Ekaterina P., primary, Sazykin, Alexey Y., primary, Penkov, Dmitry N., primary, Belousov, Pavel V., primary, Stevanović, Stefan, primary, Vass, Verona, primary, Walter, Steffen, primary, Eisel, David, primary, Schmid-Horch, Barbara D., primary, Nedospasov, Sergei A., primary, Rammensee, Hans-Georg, primary, and Gouttefangeas, Cécile, primary

Published
2023
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25. Supplementary Table 2 from Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Author

Laske, Karoline, primary, Shebzukhov, Yuriy V., primary, Grosse-Hovest, Ludger, primary, Kuprash, Dmitry V., primary, Khlgatian, Svetlana V., primary, Koroleva, Ekaterina P., primary, Sazykin, Alexey Y., primary, Penkov, Dmitry N., primary, Belousov, Pavel V., primary, Stevanović, Stefan, primary, Vass, Verona, primary, Walter, Steffen, primary, Eisel, David, primary, Schmid-Horch, Barbara D., primary, Nedospasov, Sergei A., primary, Rammensee, Hans-Georg, primary, and Gouttefangeas, Cécile, primary

Published
2023
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26. Supplementary Figure 2 from Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Author

Laske, Karoline, primary, Shebzukhov, Yuriy V., primary, Grosse-Hovest, Ludger, primary, Kuprash, Dmitry V., primary, Khlgatian, Svetlana V., primary, Koroleva, Ekaterina P., primary, Sazykin, Alexey Y., primary, Penkov, Dmitry N., primary, Belousov, Pavel V., primary, Stevanović, Stefan, primary, Vass, Verona, primary, Walter, Steffen, primary, Eisel, David, primary, Schmid-Horch, Barbara D., primary, Nedospasov, Sergei A., primary, Rammensee, Hans-Georg, primary, and Gouttefangeas, Cécile, primary

Published
2023
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27. Supplementary figure from Long-lasting Disease Stabilization in the Absence of Toxicity in Metastatic Lung Cancer Patients Vaccinated with an Epitope Derived from Indoleamine 2,3 Dioxygenase

Author

Iversen, Trine Zeeberg, primary, Engell-Noerregaard, Lotte, primary, Ellebaek, Eva, primary, Andersen, Rikke, primary, Larsen, Stine Kiaer, primary, Bjoern, Jon, primary, Zeyher, Claus, primary, Gouttefangeas, Cécile, primary, Thomsen, Birthe Moerk, primary, Holm, Bente, primary, thor Straten, Per, primary, Mellemgaard, Anders, primary, Andersen, Mads Hald, primary, and Svane, Inge Marie, primary

Published
2023
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28. Supplementary Methods and Materials from Unexpected Abundance of HLA Class II Presented Peptides in Primary Renal Cell Carcinomas

Author

Dengjel, Jörn, primary, Nastke, Maria-Dorothea, primary, Gouttefangeas, Cécile, primary, Gitsioudis, Gitsios, primary, Schoor, Oliver, primary, Altenberend, Florian, primary, Müller, Margret, primary, Krämer, Björn, primary, Missiou, Anna, primary, Sauter, Martina, primary, Hennenlotter, Jörg, primary, Wernet, Dorothee, primary, Stenzl, Arnulf, primary, Rammensee, Hans-Georg, primary, Klingel, Karin, primary, and Stevanović, Stefan, primary

Published
2023
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32. A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer

Author

Rammensee, Hans-Georg, Wiesmüller, Karl-Heinz, Chandran, P. Anoop, Zelba, Henning, Rusch, Elisa, Gouttefangeas, Cécile, Kowalewski, Daniel J., Di Marco, Moreno, Haen, Sebastian P., Walz, Juliane S., Gloria, Yamel Cardona, Bödder, Johanna, Schertel, Jill-Marie, Tunger, Antje, Müller, Luise, Kießler, Maximilian, Wehner, Rebekka, Schmitz, Marc, Jakobi, Meike, Schneiderhan-Marra, Nicole, Klein, Reinhild, Laske, Karoline, Artzner, Kerstin, Backert, Linus, Schuster, Heiko, Schwenck, Johannes, Weber, Alexander N. R., Pichler, Bernd J., Kneilling, Manfred, la Fougère, Christian, Forchhammer, Stephan, Metzler, Gisela, Bauer, Jürgen, Weide, Benjamin, Schippert, Wilfried, Stevanović, Stefan, and Löffler, Markus W.

Published
2019
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37. CTIM-17. EO2401 THERAPEUTIC VACCINE FOR PATIENTS WITH RECURRENT GLIOBLASTOMA: PHASE 1/2 ROSALIE STUDY (NCT04116658)

Author

Reardon, David A, primary, Idbaih, Ahmed, additional, Vieito, Maria, additional, Tabatabai, Ghazaleh, additional, Stradella, Agostina, additional, Ghiringhelli, François, additional, Burger, Michael C, additional, Mildenberger, Iris, additional, González, Macarena, additional, Hervieu, Alice, additional, Martin, Marta Gil, additional, Renovanz, Mirjam, additional, Touat, Mehdi, additional, Wen, Patrick Y, additional, Wick, Antje, additional, Gouttefangeas, Cécile, additional, Maia, Ana, additional, Bonny, Christophe, additional, Fagerberg, Jan, additional, and Wick, Wolfgang, additional

Published
2022
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38. 641 Strong immune response to therapeutic vaccination with EO2401 microbiome derived therapeutic vaccine + nivolumab: interim report of the EOGBM1–18/ROSALIE study

Author

Maia, Ana, primary, Toussaint, Hélène, additional, Magalhaes, Joao Gamelas, additional, Reardon, David, additional, IDBAIH, Ahmed, additional, Vieito, Maria, additional, Tabatabai, Ghazaleh, additional, Stradella, Agostina, additional, Ghiringhelli, François, additional, Burger, Michael C, additional, Mildenberger, Iris, additional, Herrlinger, Ulrich, additional, Gonzalez, Macarena, additional, Hervieu, Alice, additional, GilMartin, Marta, additional, Renovanz, Mirjam, additional, Touat, Mehdi, additional, Wen, Patrick Y, additional, Wick, Antje, additional, Chene, Laurent, additional, Gouttefangeas, Cécile, additional, Bonny, Christophe, additional, Fagerberg, Jan, additional, and Wick, Wolfgang, additional

Published
2022
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40. Booster dose of mRNA vaccine augments waning T cell and antibody responses against SARS-CoV-2

Author

Özbay Kurt, Feyza Gül, primary, Lepper, Alisa, additional, Gerhards, Catharina, additional, Roemer, Mathis, additional, Lasser, Samantha, additional, Arkhypov, Ihor, additional, Bitsch, Rebekka, additional, Bugert, Peter, additional, Altevogt, Peter, additional, Gouttefangeas, Cécile, additional, Neumaier, Michael, additional, Utikal, Jochen, additional, and Umansky, Viktor, additional

Published
2022
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41. EO2401, a novel microbiome-derived therapeutic vaccine for patients with recurrent glioblastoma: ROSALIE study.

Author

Wick, Wolfgang, primary, Idbaih, Ahmed, additional, Tabatabai, Ghazaleh, additional, Vieito, María, additional, Stradella, Agostina, additional, Ghiringhelli, François, additional, Burger, Michael C., additional, Mildenberger, Iris, additional, Herrlinger, Ulrich, additional, Renovanz, Mirjam, additional, Touat, Mehdi, additional, Wen, Patrick Y., additional, Wick, Antje, additional, Bonny, Christophe, additional, Fagerberg, Jan, additional, Gouttefangeas, Cécile, additional, Maia, Ana, additional, and Reardon, David A., additional

Published
2022
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42. Radiofrequency Ablation: The Percutaneous Approach

Author

Pereira, Philippe L., Boss, Andreas, Clasen, Stephen, Gouttefangeas, Cecile, Schmidt, Diethard, Claussen, Claus D., Schlag, P. M., editor, Senn, H. -J., editor, Kleihues, P., editor, Stiefel, F., editor, Groner, B., editor, Wallgren, A., editor, Rentchnik, P., editor, and Stroszczynski, Christian, editor

Published
2006
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45. Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma

Author

Löffler, Markus W., primary, Gori, Stefania, additional, Izzo, Francesco, additional, Mayer-Mokler, Andrea, additional, Ascierto, Paolo A., additional, Königsrainer, Alfred, additional, Ma, Yuk Ting, additional, Sangro, Bruno, additional, Francque, Sven, additional, Vonghia, Luisa, additional, Inno, Alessandro, additional, Avallone, Antonio, additional, Ludwig, Jörg, additional, Alcoba, Diego Duarte, additional, Flohr, Christian, additional, Aslan, Katrin, additional, Mendrzyk, Regina, additional, Schuster, Heiko, additional, Borrelli, Marco, additional, Valmori, Danila, additional, Chaumette, Tanguy, additional, Heidenreich, Regina, additional, Gouttefangeas, Cécile, additional, Forlani, Greta, additional, Tagliamonte, Maria, additional, Fusco, Caterina, additional, Penta, Roberta, additional, Iñarrairaegui, Mercedes, additional, Gnad-Vogt, Ulrike, additional, Reinhardt, Carsten, additional, Weinschenk, Toni, additional, Accolla, Roberto S., additional, Singh-Jasuja, Harpreet, additional, Rammensee, Hans-Georg, additional, and Buonaguro, Luigi, additional

Published
2022
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47. Single-Domain Antibodies for Targeting, Detection, and In Vivo Imaging of Human CD4+ Cells

Author

Traenkle, Bjoern, Kaiser, Philipp D., Pezzana, Stefania, Richardson, Jennifer, Gramlich, Marius, Wagner, Teresa R., Seyfried, Dominik, Weldle, Melissa, Holz, Stefanie, Parfyonova, Yana, Nueske, Stefan, Scholz, Armin M., Zeck, Anne, Jakobi, Meike, Schneiderhan-Marra, Nicole, Schaller, Martin, Maurer, Andreas, Gouttefangeas, Cécile, Kneilling, Manfred, Pichler, Bernd J., Sonanini, Dominik, and Rothbauer, Ulrich

Subjects
CD4-Positive T-Lymphocytes, Immunology, Optical Imaging, PET imaging, immunotherapies, Single-Domain Antibodies, CD4, Molecular Imaging, nanobody, Mice, magnetic resonance imaging, Animals, Heterografts, Humans, immune tracer, Original Research
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.

Published
2021

48. Staining of activated ß2-integrins in combination with CD137 and CD154 for sensitive identification of functional antigen-specific CD4+ and CD8+ T cells.

Author

Schöllhorn, Anna, Maia, Ana, Kimmerle, Felix, Born, Jan, Rammensee, Hans-Georg, Dimitrov, Stoyan, and Gouttefangeas, Cécile

Subjects
T cells, COVID-19 vaccines, SIGNAL-to-noise ratio, MONOCLONAL antibodies, CELL survival
Abstract

Common flow cytometry-based methods used for functional assessment of antigen-specific T cells rely on de novo expression of intracellular cytokines or cell surface activation induced markers. They come with some limitations such as complex experimental setting, loss of cell viability and often high unspecific background which impairs assay sensitivity. We have previously shown that staining of activated ß2-integrins either with multimers of their ligand ICAM-1 or with a monoclonal antibody can serve as a functional marker detectable on T cells after minutes (CD8+) or few hours (CD4+) of activation. Here, we present a simple method for detection of activated ß2-integrins in combination with established cell surface activation induced markers. We observed that activated ß2-integrins were still detectable after 14 hours of stimulation, allowing their detection together with CD137 and CD154. Combinatorial gating of cells expressing activated ß2-integrins and CD137 or CD154 reduced background in unstimulated samples, increasing the signal-to-noise ratio and allowing improved assessment of low-frequency T cell responses. Extracellular staining of these markers highly correlated with production of intracellular cytokines IL-2, TNF or IFNg in CD4+ and CD8+ T cells. As an exemplary application, SARS-CoV-2 spike-specific T cell responses were assessed in individuals after COVID-19 vaccination. This method should be useful for epitope discovery projects and for the simultaneous monitoring of lowfrequency antigen-specific CD4+ and CD8+ T cell responses in various physiological situations. [ABSTRACT FROM AUTHOR]

Published
2023
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