Caractérisation d'anticorps neutralisants réagissant avec le segment des acides aminés 213-224 de la galectine-9 humaine

Autor: Claire Lhuillier, Clément Barjon, Valentin Baloche, Toshiro Niki, Aurore Gelin, Rami Mustapha, Laetitia Claër, Sylviane Hoos, Yoichi Chiba, Masaki Ueno, Mitsuomi Hirashima, Ming Wei, Olivier Morales, Bertrand Raynal, Nadira Delhem, Olivier Dellis, Pierre Busson
Přispěvatelé: Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Kagawa University [Japan], Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), H-Immune Therapeutics [Paris], Biophysique Moléculaire (Plate-forme), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Cellvax, École nationale vétérinaire d'Alfort (ENVA), Intéractions cellulaires et physiopathologie hépathique (Orsay, Essonne) UMRS 1174 (ICPH ), Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Idex Saclay - Satt Saclay, Prematuration Grant 2015, https://www.satt-paris-saclay.fr, BMS Foundation for Immuno-Oncology- Grant 2016-2017, http://fondation-bms.fr/. Several authors were employed by commercial companies: Cellvax (CL, CB, MW)
Rok vydání: 2018
Předmět:
MESH: T-Lymphocytes/metabolism
MESH: Apoptosis/drug effects
MESH: Biological Transport
[SDV]Life Sciences [q-bio]
Galectins
T-Lymphocytes
MESH: T-Lymphocytes/drug effects
MESH: Galectins/adverse effects
lcsh:Medicine
Lactose
MESH: Galectins/immunology
[SDV.CAN]Life Sciences [q-bio]/Cancer
Apoptosis
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Phosphatidylserines
MESH: Antibodies
Neutralizing/pharmacology
Antibodies
Epitopes
Jurkat Cells
Mice
MESH: T-Lymphocytes/cytology
MESH: Jurkat Cells
Animals
Humans
MESH: Animals
Flow cytometry
Enzyme-linked immunoassays
lcsh:Science
MESH: Mice
MESH: Antibodies
Monoclonal/pharmacology
Antibody isotypes
MESH: Humans
lcsh:R
MESH: Calcium/metabolism
Antibodies
Monoclonal
Biological Transport
MESH: Epitopes/immunology
Cell staining
Antibodies
Neutralizing
MESH: Galectins/chemistry
Apoptosis T cells
MESH: Immunization
[SDV.IMM]Life Sciences [q-bio]/Immunology
lcsh:Q
Calcium
Immunization
MESH: Phosphatidylserines/metabolism
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2018, 13 (9), pp.e0202512. ⟨10.1371/journal.pone.0202512⟩
PLoS ONE, Vol 13, Iss 9, p e0202512 (2018)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0202512⟩
Popis: International audience; Extra-cellular galectin-9 (gal-9) is an immuno-modulatory protein with predominant immuno-suppressive effects. Inappropriate production of gal-9 has been reported in several human malignancies and viral diseases like nasopharyngeal, pancreatic and renal carcinomas, metastatic melanomas and chronic active viral hepatitis. Therefore therapeutic antibodies neutralizing extra-cellular gal-9 are expected to contribute to immune restoration in these pathological conditions. Two novel monoclonal antibodies targeting gal-9-Gal-Nab 1 and 2-have been produced and characterized in this study. We report a protective effect of Gal-Nab1 and Gal-Nab2 on the apoptotic cell death induced by gal-9 in primary T cells. In addition, they inhibit late phenotypic changes observed in peripheral T cells that survive gal-9-induced apoptosis. Gal-Nab1 and Gal-Nab2 bind nearly identical, overlapping linear epi-topes contained in the 213-224 amino-acid segments of gal-9. Nevertheless, they have some distinct functional characteristics suggesting that their three-dimensional epitopes are distinct. These differences are best demonstrated when gal-9 is applied on Jurkat cells where Gal-Nab1 is less efficient than Gal-Nab2 in the prevention of apoptotic cell death. In addition, Gal-Nab1 stimulates non-lethal phosphatidylserine translocation at the plasma membrane and calcium mobilization triggered by gal-9 in these cells. Both Gal-Nab1 and 2 cross-react with murine gal-9. They bind its natural as well as its recombinant form. This cross-species recognition will be an advantage for their assessment in pre-clinical tumor models.
Databáze: OpenAIRE
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