20 results on '"Lopez-Lastra, Silvia"'
Search Results
2. Supplementary Data from Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer
- Author
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Timperi, Eleonora, primary, Gueguen, Paul, primary, Molgora, Martina, primary, Magagna, Ilaria, primary, Kieffer, Yann, primary, Lopez-Lastra, Silvia, primary, Sirven, Philemon, primary, Baudrin, Laura G., primary, Baulande, Sylvain, primary, Nicolas, André, primary, Champenois, Gabriel, primary, Meseure, Didier, primary, Vincent-Salomon, Anne, primary, Tardivon, Anne, primary, Laas, Enora, primary, Soumelis, Vassili, primary, Colonna, Marco, primary, Mechta-Grigoriou, Fatima, primary, Amigorena, Sebastian, primary, and Romano, Emanuela, primary
- Published
- 2023
- Full Text
- View/download PDF
3. NK Cell Development in Human Immune System (HIS) Mice and Their Role in HIV Pathogenesis
- Author
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Li, Yan, Lopez-Lastra, Silvia, Masse, Guillemette X., Di Santo, James P., Poluektova, Larisa Y., editor, Garcia, J. Victor, editor, Koyanagi, Yoshio, editor, Manz, Markus G., editor, and Tager, Andrew M., editor
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- 2014
- Full Text
- View/download PDF
4. Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer
- Author
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Timperi, Eleonora, primary, Gueguen, Paul, additional, Molgora, Martina, additional, Magagna, Ilaria, additional, Kieffer, Yann, additional, Lopez-Lastra, Silvia, additional, Sirven, Philemon, additional, Baudrin, Laura G., additional, Baulande, Sylvain, additional, Nicolas, André, additional, Champenois, Gabriel, additional, Meseure, Didier, additional, Vincent-Salomon, Anne, additional, Tardivon, Anne, additional, Laas, Enora, additional, Soumelis, Vassili, additional, Colonna, Marco, additional, Mechta-Grigoriou, Fatima, additional, Amigorena, Sebastian, additional, and Romano, Emanuela, additional
- Published
- 2022
- Full Text
- View/download PDF
5. Abstract 1615: Immune-related adverse effects (irAEs) associated proteomic profile in late-stage NSCLC patients after PD-1 blockade
- Author
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Sklodowski, Kamil, primary, Dozio, Vito, additional, Poli, Roberta, additional, Lanzós, Andrés, additional, Lopez-Lastra, Silvia, additional, Beeler, Kristina, additional, and Romano, Emanuela, additional
- Published
- 2021
- Full Text
- View/download PDF
6. 59 Integrating deep proteomics profiling with survival analysis to identify novel biomarkers of response to PD-1 blockade in NSCLC patients
- Author
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Sklodowski, Kamil, primary, Dozio, Vito, additional, Lopez-Lastra, Silvia, additional, Lanzós, Andrés, additional, Beeler, Kristina, additional, and Romano, Emanuela, additional
- Published
- 2020
- Full Text
- View/download PDF
7. Evaluation of blood-based proteomic biomarkers associated with response to anti-PD-1 treatment in NSCLC.
- Author
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Dupuis, Nicholas, primary, Lopez-Lastra, Silvia, additional, Dumont, Clement, additional, Dozio, Vito, additional, Beeler, Kristina, additional, Sklodowski, Kamil, additional, and Romano, Emanuela, additional
- Published
- 2020
- Full Text
- View/download PDF
8. Accelerated thymopoiesis and improved T‐cell responses in HLA‐A2/‐DR2 transgenic BRGS‐based human immune system mice
- Author
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Masse‐Ranson, Guillemette, primary, Dusséaux, Mathilde, additional, Fiquet, Oriane, additional, Darche, Sylvie, additional, Boussand, Maud, additional, Li, Yan, additional, Lopez‐Lastra, Silvia, additional, Legrand, Nicolas, additional, Corcuff, Erwan, additional, Toubert, Antoine, additional, Centlivre, Mireille, additional, Bruel, Timothée, additional, Spits, Hergen, additional, Schwartz, Olivier, additional, Lévy, Yves, additional, Strick‐Marchand, Hélène, additional, and Di Santo, James P., additional
- Published
- 2019
- Full Text
- View/download PDF
9. Modeling Natural Killer Cell Targeted Immunotherapies
- Author
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Lopez-Lastra, Silvia and Di Santo, James P.
- Subjects
humanized mouse models ,natural killer cells ,cancer immunotherapy ,natural killer cell immunotherapy ,Immunology ,innate lymphoid cell - Abstract
Animal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of diseases. However, mouse models do not reproduce the genetic and molecular complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis and tumor immunobiology provide one means to bridge the interspecies gap. Natural killer cells are the founding member of the innate lymphoid cell family. They exert a rapid and strong immune response against tumor and pathogen-infected cells. Their antitumor features have long been exploited for therapeutic purposes in the context of cancer. In this review, we detail the development of highly immunodeficient mouse strains and the models currently used in cancer research. We summarize the latest improvements in adoptive natural killer (NK) cell therapies and the development of novel NK cell sources. Finally, we discuss the advantages of HIS mice to study the interactions between human NK cells and human cancers and to develop new therapeutic strategies.
- Published
- 2017
- Full Text
- View/download PDF
10. Les souris humanisées comme modèles d'étude de l'immunité innée humaine et des immunothérapies
- Author
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Lopez-Lastra, Silvia, Institut Pasteur [Paris], Université Paris-Saclay, James P. Di Santo, and Nathalie Sauvonnet
- Subjects
Human immune system mice ,Natural killer ,Immunothérapies ,Innate lymphoid cells ,Immunotherapy ,Cellules lymphoïdes innées ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Souris humanisées - Abstract
Animal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of the disease. However, mouse models do not always reproduce the genetic complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis provide one means to bridge the interspecies gap. Severely immunodeficient host mice support life-long, high level human hematolymphoid development after engraftment with human hematopoietic stem cells (HSC). However, the differentiation and function of some blood cell types, including innate lymphoid cells (ILCs), is poorly characterized in current HIS mice. Here we describe the development of a novel HIS mouse model, named BRGSF, which demonstrate enhanced maturation, function and homeostasis of human natural killer (NK) cells and other ILCs. Furthermore, the BRGSF-based HIS mouse model recapitulated the developmental stages of human ILCs. We could identify for the first time an ILC precursor (ILCP) population that is present both in HIS mice and in human peripheral blood as well as in several lymphoid and non-lymphoid human tissues. This circulating human ILCP population may provide a substrate to generate mature ILCs in tissues in response to environmental stressors, inflammation and infection. In a second part of the thesis we used BRGS immunodeficient mice to assess two innate lymphocyte-based immunotherapeutic approaches for treating EGFR-expressing KRAS-mutated colorectal carcinoma in vivo. The first model used a combination of umbilical cord blood (UCB)-derived NK cells and the monoclonal antibody cetuximab to promote antibody dependent cell cytotoxicity (ADCC) against the tumors. In a second model, we evaluated the therapeutic suitability of novel bispecific VHH constructs that combine inhibition of the EGFR with the target-specific activation of effector Vγ9Vδ2-T cells. These studies highlight the utility for HIS-based mouse models to understand human innate lymphocyte development and to harness these potent effectors for anti-tumor therapies.; Les modèles animaux ont largement contribué à notre compréhension de l’immunologie humaine et des mécanismes pathologiques associés au développement des maladies. Cependant, les modèles murins ne permettent pas de reproduire toute la complexité des pathologies humaines. Les souris à système immunitaire humain (HIS), par leur capacité à récapituler l’hématopoïèse humaine et à être infectées par des pathogènes humains, constituent une solution de choix pour combler ce fossé inter-espèce. Après greffe de cellules souches hématopoïétiques humaines, des souris hôtes sévèrement immunodéprimées permettent un haut niveau de développement du système hémato-lymphoïde humain tout au long de leur vie. Cependant, certains types cellulaires, comme les cellules lymphoïdes innées, ne parviennent pas à se différencier et à fonctionner normalement dans les modèles murins HIS actuels. Ici, nous décrivons le développement d’un modèle souris HIS original, nommé BRGSF, montrant une amélioration de la maturation, de la fonction et de l’homéostasie des cellules natural killer (NK) humaines et des autres ILCs. De plus, en récapitulant les différentes étapes du développement des ILCs humaines, ce modèle souris BRGSF nous a permis d’identifier pour la première fois un précurseur d’ILC (ILCP) présent à la fois dans notre modèle HIS ainsi que dans le sang périphérique et plusieurs organes lymphoïdes et non-lymphoïdes humains. Cette population circulante d’ILCPs pourrait constituer un substrat pour la production d’ILCs matures dans les tissus périphériques en réponse à des stress environnementaux, inflammatoires et/ou infectieux. Dans une seconde partie de ce travail de thèse, nous avons utilisé ces souris BRGS afin de tester l’efficacité de deux immunothérapies reposant sur les lymphocytes innés pour le traitement d’un carcinome colorectal exprimant EGFR et muté pour KRAS. La première approche a consisté en la co-administration des cellules NK dérivées de sang de cordon ombilical et d'anticorps monoclonal cetuximab afin de promouvoir le mécanisme de cytotoxicité cellulaire dépendante des anticorps (ADCC) contre la tumeur. La seconde stratégie a reposé sur l’injection de nanobodies VHH combinant l’inhibition de l’EGFR et l’activation spécifique du récepteur Vγ9Vδ2 des cellules T effectrices. Les résultats de cette étude soulignent l’importance des modèles murins HIS pour la compréhension du développement des lymphocytes innés humains et pour mieux les mettre à profit dans les thérapies anti-tumeurs
- Published
- 2017
11. Humanized Mice as Models to study Human Innate Immunity and Immunotherapies
- Author
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Lopez-Lastra, Silvia, Institut Pasteur [Paris] (IP), Université Paris-Saclay, James P. Di Santo, Nathalie Sauvonnet, and Institut Pasteur [Paris]
- Subjects
Human immune system mice ,Natural killer ,Immunothérapies ,Innate lymphoid cells ,Immunotherapy ,Cellules lymphoïdes innées ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Souris humanisées - Abstract
Animal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of the disease. However, mouse models do not always reproduce the genetic complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis provide one means to bridge the interspecies gap. Severely immunodeficient host mice support life-long, high level human hematolymphoid development after engraftment with human hematopoietic stem cells (HSC). However, the differentiation and function of some blood cell types, including innate lymphoid cells (ILCs), is poorly characterized in current HIS mice. Here we describe the development of a novel HIS mouse model, named BRGSF, which demonstrate enhanced maturation, function and homeostasis of human natural killer (NK) cells and other ILCs. Furthermore, the BRGSF-based HIS mouse model recapitulated the developmental stages of human ILCs. We could identify for the first time an ILC precursor (ILCP) population that is present both in HIS mice and in human peripheral blood as well as in several lymphoid and non-lymphoid human tissues. This circulating human ILCP population may provide a substrate to generate mature ILCs in tissues in response to environmental stressors, inflammation and infection. In a second part of the thesis we used BRGS immunodeficient mice to assess two innate lymphocyte-based immunotherapeutic approaches for treating EGFR-expressing KRAS-mutated colorectal carcinoma in vivo. The first model used a combination of umbilical cord blood (UCB)-derived NK cells and the monoclonal antibody cetuximab to promote antibody dependent cell cytotoxicity (ADCC) against the tumors. In a second model, we evaluated the therapeutic suitability of novel bispecific VHH constructs that combine inhibition of the EGFR with the target-specific activation of effector Vγ9Vδ2-T cells. These studies highlight the utility for HIS-based mouse models to understand human innate lymphocyte development and to harness these potent effectors for anti-tumor therapies.; Les modèles animaux ont largement contribué à notre compréhension de l’immunologie humaine et des mécanismes pathologiques associés au développement des maladies. Cependant, les modèles murins ne permettent pas de reproduire toute la complexité des pathologies humaines. Les souris à système immunitaire humain (HIS), par leur capacité à récapituler l’hématopoïèse humaine et à être infectées par des pathogènes humains, constituent une solution de choix pour combler ce fossé inter-espèce. Après greffe de cellules souches hématopoïétiques humaines, des souris hôtes sévèrement immunodéprimées permettent un haut niveau de développement du système hémato-lymphoïde humain tout au long de leur vie. Cependant, certains types cellulaires, comme les cellules lymphoïdes innées, ne parviennent pas à se différencier et à fonctionner normalement dans les modèles murins HIS actuels. Ici, nous décrivons le développement d’un modèle souris HIS original, nommé BRGSF, montrant une amélioration de la maturation, de la fonction et de l’homéostasie des cellules natural killer (NK) humaines et des autres ILCs. De plus, en récapitulant les différentes étapes du développement des ILCs humaines, ce modèle souris BRGSF nous a permis d’identifier pour la première fois un précurseur d’ILC (ILCP) présent à la fois dans notre modèle HIS ainsi que dans le sang périphérique et plusieurs organes lymphoïdes et non-lymphoïdes humains. Cette population circulante d’ILCPs pourrait constituer un substrat pour la production d’ILCs matures dans les tissus périphériques en réponse à des stress environnementaux, inflammatoires et/ou infectieux. Dans une seconde partie de ce travail de thèse, nous avons utilisé ces souris BRGS afin de tester l’efficacité de deux immunothérapies reposant sur les lymphocytes innés pour le traitement d’un carcinome colorectal exprimant EGFR et muté pour KRAS. La première approche a consisté en la co-administration des cellules NK dérivées de sang de cordon ombilical et d'anticorps monoclonal cetuximab afin de promouvoir le mécanisme de cytotoxicité cellulaire dépendante des anticorps (ADCC) contre la tumeur. La seconde stratégie a reposé sur l’injection de nanobodies VHH combinant l’inhibition de l’EGFR et l’activation spécifique du récepteur Vγ9Vδ2 des cellules T effectrices. Les résultats de cette étude soulignent l’importance des modèles murins HIS pour la compréhension du développement des lymphocytes innés humains et pour mieux les mettre à profit dans les thérapies anti-tumeurs
- Published
- 2017
12. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells
- Author
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de Bruin, Renée C. G., primary, Veluchamy, John P., additional, Lougheed, Sinéad M., additional, Schneiders, Famke L., additional, Lopez-Lastra, Silvia, additional, Lameris, Roeland, additional, Stam, Anita G., additional, Sebestyen, Zsolt, additional, Kuball, Jürgen, additional, Molthoff, Carla F. M., additional, Hooijberg, Erik, additional, Roovers, Rob C., additional, Santo, James P. Di, additional, van Bergen en Henegouwen, Paul M. P., additional, Verheul, Henk M. W., additional, de Gruijl, Tanja D., additional, and van der Vliet, Hans J., additional
- Published
- 2017
- Full Text
- View/download PDF
13. A functional DC cross talk promotes human ILC homeostasis in humanized mice
- Author
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Lopez-Lastra, Silvia, primary, Masse-Ranson, Guillemette, additional, Fiquet, Oriane, additional, Darche, Sylvie, additional, Serafini, Nicolas, additional, Li, Yan, additional, Dusséaux, Mathilde, additional, Strick-Marchand, Helene, additional, and Di Santo, James P., additional
- Published
- 2017
- Full Text
- View/download PDF
14. Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation
- Author
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Lim, Ai Ing, primary, Li, Yan, additional, Lopez-Lastra, Silvia, additional, Stadhouders, Ralph, additional, Paul, Franziska, additional, Casrouge, Armanda, additional, Serafini, Nicolas, additional, Puel, Anne, additional, Bustamante, Jacinta, additional, Surace, Laura, additional, Masse-Ranson, Guillemette, additional, David, Eyal, additional, Strick-Marchand, Helene, additional, Le Bourhis, Lionel, additional, Cocchi, Roberto, additional, Topazio, Davide, additional, Graziano, Paolo, additional, Muscarella, Lucia Anna, additional, Rogge, Lars, additional, Norel, Xavier, additional, Sallenave, Jean-Michel, additional, Allez, Matthieu, additional, Graf, Thomas, additional, Hendriks, Rudi W., additional, Casanova, Jean-Laurent, additional, Amit, Ido, additional, Yssel, Hans, additional, and Di Santo, James P., additional
- Published
- 2017
- Full Text
- View/download PDF
15. In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer
- Author
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Veluchamy, John P., primary, Lopez-Lastra, Silvia, additional, Spanholtz, Jan, additional, Bohme, Fenna, additional, Kok, Nina, additional, Heideman, Daniëlle A. M., additional, Verheul, Henk M. W., additional, Di Santo, James P., additional, de Gruijl, Tanja D., additional, and van der Vliet, Hans J., additional
- Published
- 2017
- Full Text
- View/download PDF
16. Interleukin-15-Dependent T-Cell-like Innate Intraepithelial Lymphocytes Develop in the Intestine and Transform into Lymphomas in Celiac Disease
- Author
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Ettersperger, Julien, primary, Montcuquet, Nicolas, additional, Malamut, Georgia, additional, Guegan, Nicolas, additional, Lopez-Lastra, Silvia, additional, Gayraud, Ségolène, additional, Reimann, Christian, additional, Vidal, Elodie, additional, Cagnard, Nicolas, additional, Villarese, Patrick, additional, Andre-Schmutz, Isabelle, additional, Gomes Domingues, Rita, additional, Godinho-Silva, Cristina, additional, Veiga-Fernandes, Henrique, additional, Lhermitte, Ludovic, additional, Asnafi, Vahid, additional, Macintyre, Elizabeth, additional, Cellier, Christophe, additional, Beldjord, Kheira, additional, Di Santo, James P., additional, Cerf-Bensussan, Nadine, additional, and Meresse, Bertrand, additional
- Published
- 2016
- Full Text
- View/download PDF
17. Human thymopoiesis is influenced by a common genetic variant within the TCRA-TCRD locus.
- Author
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Clave, Emmanuel, Araujo, Itauá Leston, Alanio, Cécile, Patin, Etienne, Bergstedt, Jacob, Urrutia, Alejandra, Lopez-Lastra, Silvia, Li, Yan, Charbit, Bruno, MacPherson, Cameron Ross, Hasan, Milena, Melo-Lima, Breno Luiz, Douay, Corinne, Saut, Noémie, Germain, Marine, Trégouët, David-Alexandre, Morange, Pierre-Emmanuel, Fontes, Magnus, Duffy, Darragh, and Di Santo, James P.
- Subjects
HUMAN genetic variation ,T cell receptors ,LABORATORY mice ,HUMAN gene mapping ,HUMAN genome - Abstract
Aging, sex, and genetics substantially affect human thymic function. Mining the Milieu Intérieur: Personalized medicine partly depends on understanding what causes variance even outside the context of overt disease. The Milieu Intérieur Consortium enrolled 1000 healthy adults to study how genetics and the environment influence the immune system. Clave et al. leveraged samples from this cohort to see how thymic output, known to decrease over time, is affected by other factors. In addition to seeing sex-dependent differences, a genome-wide association study revealed variants that were associated with thymic output, which was confirmed in an independent cohort and mouse models. The authors have also developed a Web application for other investigators to examine the Milieu Intérieur data. The thymus is the primary lymphoid organ where naïve T cells are generated; however, with the exception of age, the parameters that govern its function in healthy humans remain unknown. We characterized the variability of thymic function among 1000 age- and sex-stratified healthy adults of the Milieu Intérieur cohort, using quantification of T cell receptor excision circles (TRECs) in peripheral blood T cells as a surrogate marker of thymopoiesis. Age and sex were the only nonheritable factors identified that affect thymic function. TREC amounts decreased with age and were higher in women compared to men. In addition, a genome-wide association study revealed a common variant (rs2204985) within the T cell receptor TCRA-TCRD locus, between the DD2 and DD3 gene segments, which associated with TREC amounts. Strikingly, transplantation of human hematopoietic stem cells with the rs2204985 GG genotype into immunodeficient mice led to thymopoiesis with higher TRECs, increased thymocyte counts, and a higher TCR repertoire diversity. Our population immunology approach revealed a genetic locus that influences thymopoiesis in healthy adults, with potentially broad implications in precision medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
18. MOSAIC: Multi-Omic Spatial Atlas in Cancer, effect on precision oncology.
- Author
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Lehar, Joseph, Madissoon, Elo, Chevallier, Jerome, Schiratti, Jean Baptiste, Kamburov, Atanas, Barnes, Rodrigo, Haignere, Carla, Joy, Anna, Dodacki, Agnès, Hoffmann, Caroline, Lopez Lastra, Silvia, Espin Perez, Almudena, Bayard, Quentin, von Loga, Katharina, Chaperon, Hubert, Vert, Jean-Philippe, Durand, Eric, Soumelis, Vassili, Wainrib, Gilles, and Clozel, Thomas
- Published
- 2023
- Full Text
- View/download PDF
19. NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors
- Author
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Xu, Wei, primary, Domingues, Rita G., additional, Fonseca-Pereira, Diogo, additional, Ferreira, Manuela, additional, Ribeiro, Hélder, additional, Lopez-Lastra, Silvia, additional, Motomura, Yasutaka, additional, Moreira-Santos, Lara, additional, Bihl, Franck, additional, Braud, Véronique, additional, Kee, Barbara, additional, Brady, Hugh, additional, Coles, Mark C., additional, Vosshenrich, Christian, additional, Kubo, Masato, additional, Di Santo, James P., additional, and Veiga-Fernandes, Henrique, additional
- Published
- 2015
- Full Text
- View/download PDF
20. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells.
- Author
-
de Bruin, Renée C. G., Veluchamy, John P., Lougheed, Sinéad M., Schneiders, Famke L., Lopez-Lastra, Silvia, Lameris, Roeland, Stam, Anita G., Sebestyen, Zsolt, Kuball, Jürgen, Molthoff, Carla F. M., Hooijberg, Erik, Roovers, Rob C., Santo, James P. Di, van Bergen en Henegouwen, Paul M. P., Verheul, Henk M. W., de Gruijl, Tanja D., and van der Vliet, Hans J.
- Subjects
CANCER immunotherapy ,T cells ,CANCER treatment ,THERAPEUTICS - Abstract
Though Vγ9Vδ2-T cells constitute only a small fraction of the total T cell population in human peripheral blood, they play a vital role in tumor defense and are therefore of major interest to explore for cancer immunotherapy. Vγ9Vδ2-T cell-based cancer immunotherapeutic approaches developed so far have been generally well tolerated and were able to induce significant clinical responses. However, overall results were inconsistent, possibly due to the fact that these strategies induced systemic activation of Vγ9Vδ2-T cells without preferential accumulation and targeted activation in the tumor. Here we show that a novel bispecific nanobody-based construct targeting both Vγ9Vδ2-T cells and EGFR induced potent Vγ9Vδ2-T cell activation and subsequent tumor cell lysis bothin vitroand in anin vivomouse xenograft model. Tumor cell lysis was independent ofKRASandBRAFtumor mutation status and common Vγ9Vδ2-T cell receptor sequence variations. In combination with the conserved monomorphic nature of the Vγ9Vδ2-TCR and the facile replacement of the tumor-specific nanobody, this immunotherapeutic approach can be applied to a large group of cancer patients. [ABSTRACT FROM PUBLISHER]
- Published
- 2018
- Full Text
- View/download PDF
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