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  1. Article ; Online: Dynamic human immune and tumour cells cross-talk in PDX-humanised mice warrants checkpoint inhibitor cancer immunotherapies assessment.

    Poirier, Nicolas / Vanhove, Bernard

    Gut

    2018  Volume 67, Issue 10, Page(s) 1753–1754

    MeSH term(s) Animals ; CTLA-4 Antigen ; Cross Reactions ; Humans ; Immunotherapy ; Mice ; Neoplasms
    Chemical Substances CTLA-4 Antigen
    Language English
    Publishing date 2018-04-26
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80128-8
    ISSN 1468-3288 ; 0017-5749
    ISSN (online) 1468-3288
    ISSN 0017-5749
    DOI 10.1136/gutjnl-2018-316467
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  2. Article ; Online: Corneal Xenotransplantation: Anterior Lamellar Keratoplasty.

    Vabres, Bertrand / Vanhove, Bernard / Blancho, Gilles

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2110, Page(s) 245–251

    Abstract: Corneal transplantation for the treatment of corneal blindness is challenging in many countries due to the shortage of graft procurement. Xenocorneal transplantation is an interesting alternative to explore despite immunologic rejection, which mainly ... ...

    Abstract Corneal transplantation for the treatment of corneal blindness is challenging in many countries due to the shortage of graft procurement. Xenocorneal transplantation is an interesting alternative to explore despite immunologic rejection, which mainly involves endothelial cells. As anterior lamellar keratoplasty, when indicated, shows less immunologic reaction, we developed and describe below a pig-to-non-human-primate model of anterior lamellar corneal xenograft. This model can be used to assess the efficacy of corneas from genetically modified pigs.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Corneal Diseases/etiology ; Corneal Diseases/surgery ; Corneal Transplantation/adverse effects ; Corneal Transplantation/methods ; Graft Survival/immunology ; Heterografts ; Macaca fascicularis ; Male ; Postoperative Care ; Swine ; Transplantation, Heterologous/adverse effects ; Transplantation, Heterologous/methods
    Language English
    Publishing date 2020-01-30
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0255-3_16
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  3. Article ; Online: A novel assay based on pre-equilibrium titration curves for the determination of enzyme inhibitor binding kinetics.

    Noppen, Bernard / Vanbelle, Anouk / Stitt, Alan W / Vanhove, Marc

    European biophysics journal : EBJ

    2021  Volume 50, Issue 7, Page(s) 1037–1043

    Abstract: Selection of pharmacological agents based on potency measurements performed at equilibrium fail to incorporate the kinetic aspects of the drug-target interaction. Here we describe a method for screening or characterization of enzyme inhibitors that ... ...

    Abstract Selection of pharmacological agents based on potency measurements performed at equilibrium fail to incorporate the kinetic aspects of the drug-target interaction. Here we describe a method for screening or characterization of enzyme inhibitors that allows the concomitant determination of the equilibrium inhibition constant in unison with rates of complex formation and dissociation. The assay is distinct from conventional enzymatic assays and is based on the analysis of inhibition curves recorded prior to full equilibration of the system. The methodology is illustrated using bicyclic peptide inhibitors of the serine protease plasma kallikrein.
    MeSH term(s) Enzyme Inhibitors/pharmacology ; Kinetics ; Protein Binding ; Serine Endopeptidases
    Chemical Substances Enzyme Inhibitors ; Serine Endopeptidases (EC 3.4.21.-)
    Language English
    Publishing date 2021-06-22
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 283671-3
    ISSN 1432-1017 ; 0175-7571
    ISSN (online) 1432-1017
    ISSN 0175-7571
    DOI 10.1007/s00249-021-01554-0
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  4. Article ; Online: Les futures générations d’anticorps modulateurs des points de contrôle de la réponse immunitaire.

    Bonnefoy, Nathalie / Olive, Daniel / Vanhove, Bernard

    Medecine sciences : M/S

    2020  Volume 35, Issue 12, Page(s) 966–974

    Abstract: Immune checkpoints balance initial antigen-driven T cell stimulation by enhancing or dampening activation, allowing co-existence of efficient immune responses and maintenance of self-tolerance. In oncology, checkpoints currently targeted by inhibitors to ...

    Title translation Next generation of anti-immune checkpoints antibodies.
    Abstract Immune checkpoints balance initial antigen-driven T cell stimulation by enhancing or dampening activation, allowing co-existence of efficient immune responses and maintenance of self-tolerance. In oncology, checkpoints currently targeted by inhibitors to amplify activity of T cell, NK cells or myeloid cells responses comprise CTLA-4 (cytolytic T-lymphocyte-associated antigen 4 or CD152), PD-1 (programmed cell death 1, or CD279), PD-L1 ( programmed cell death-ligand 1, or CD274), LAG-3 (Lymphocyte-activation gene 3, or CD223), TIM3 (T-cell immunoglobulin and mucin-domain containing-3), TIGIT (T cell immunoreceptor with Ig and ITIM domains ), VISTA (V-domain Ig suppressor of T cell activation), B7/H3 (or CD276), KIR (killer-cell immunoglobulin-like receptor), NKG2A, CD39, CD73, CSF1R (colony-stimulating factor 1 receptor), CD47 or CD172a. Other "checkpoints" are being pharmacologically triggered in order to directly amplify T cell co-stimulation. Among these molecules, CD28, CD137 (also called 4-1BB), OX40 [also called tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], GITR (Glucocorticoid-induced tumor necrosis factor receptor family-related protein) or CD40 are also tested in oncology, most often in combination with an inhibitory checkpoint inhibitor. In autoimmune and inflammatory diseases, checkpoint inhibitors or activators (LAG-3, CD28, CD40L) are also being tested. In this review, we focus on some modulators of immune checkpoints for which the mechanism of action has been particularly studied. As this description cannot be exhaustive, we have grouped in Table I all monoclonal antibodies (MAbs) or recombinant proteins in clinical use (to our knowledge), modulating the action of a control point of the immune system.
    MeSH term(s) Animals ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Checkpoints/immunology ; Humans ; Immunologic Factors/therapeutic use ; Immunotherapy/methods ; Immunotherapy/trends ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents, Immunological ; Immunologic Factors ; Protein Kinase Inhibitors
    Language French
    Publishing date 2020-01-06
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 632733-3
    ISSN 1958-5381 ; 0767-0974
    ISSN (online) 1958-5381
    ISSN 0767-0974
    DOI 10.1051/medsci/2019193
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  5. Article ; Online: Polyclonal antibodies selectively inhibit tumor growth and invasion and synergize with immune checkpoint inhibitors.

    Ciron, Carine / Morice, Pierre / Rousse, Juliette / Roy, Patrice / Royer, Pierre-Joseph / Gauthier, Olivier / Brouard, Sophie / Duvaux, Odile / Bassissi, Firas / Vanhove, Bernard

    JCI insight

    2024  Volume 9, Issue 3

    Abstract: Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent preclinical models confirmed pAb efficacy, though their ability to tackle complex target antigens reduces ... ...

    Abstract Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent preclinical models confirmed pAb efficacy, though their ability to tackle complex target antigens reduces susceptibility to tumor escape. Owing to the recent availability of glyco-humanized pAb (GH-pAb) with acceptable clinical toxicology profile, we revisited use of pAb in oncology and highlighted their therapeutic potential against multiple cancer types. Murine antitumor pAb were generated after repeated immunization of rabbits with murine tumor cell lines from hepatocarcinoma, melanoma, and colorectal cancers. Antitumor pAb recognized and showed cytotoxicity against their targets without cross-reactivity with healthy tissues. In vivo, pAb are effective alone; moreover, these pAb synergize with immune checkpoint inhibitors like anti-PD-L1 in several cancer models. They elicited an antitumor host immune response and prevented metastases. The anticancer activity of pAb was also confirmed in xenografted NMRI nude mice using GH-pAb produced by repeated immunization of pigs with human tumor cell lines. In conclusion, the availability of bioengineered GH-pAb allows for revisiting of passive immunotherapy with oncolytic pAb to fight against solid tumor and cancer metastasis.
    MeSH term(s) Humans ; Rabbits ; Animals ; Mice ; Swine ; Immune Checkpoint Inhibitors ; Mice, Nude ; Immunization ; Melanoma/therapy ; Cell Line, Tumor ; Antibodies, Neoplasm/pharmacology
    Chemical Substances Immune Checkpoint Inhibitors ; Antibodies, Neoplasm
    Language English
    Publishing date 2024-02-08
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.166231
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  6. Article ; Online: First-in-human Study With LIS1, a Next-generation Porcine Low Immunogenicity Antilymphocyte Immunoglobulin in Kidney Transplantation.

    Viklicky, Ondrej / Slatinska, Janka / Janousek, Libor / Rousse, Juliette / Royer, Pierre-Joseph / Toutain, Pierre-Louis / Cozzi, Emanuele / Galli, Cesare / Evanno, Gwenaelle / Duvaux, Odile / Bach, Jean-Marie / Soulillou, Jean-Paul / Giral, Magali / Vanhove, Bernard / Blancho, Gilles

    Transplantation

    2024  

    Abstract: Background: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti-N-glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted ...

    Abstract Background: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti-N-glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models.
    Methods: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg.
    Results: CD3+ T cell depletion <100/mm3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected.
    Conclusions: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004967
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    Zs.A 488: Show issues Location:
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    Zs.MO 509: Show issues

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  7. Article: Anticorps monoclonaux en transplantation.

    Vanhove, Bernard

    Medecine sciences : M/S

    2009  Volume 25, Issue 12, Page(s) 1121–1125

    Abstract: Polyclonal anti-lymphoyctes antibodies were first successfully used in the 1970 in organ transplantation, but ten years later, monoclonal antibodies (mAb) emerged as a new class of immunosuppressive agents in transplantation with the potential to target ... ...

    Title translation Monoclonal antibodies in organ transplantation.
    Abstract Polyclonal anti-lymphoyctes antibodies were first successfully used in the 1970 in organ transplantation, but ten years later, monoclonal antibodies (mAb) emerged as a new class of immunosuppressive agents in transplantation with the potential to target highly specifically immune cells responsible for acute rejection. Some have proved their efficacy, such as mAb recognizing CD3- and CD25-positive T cells and have been extensively studied in clinical trials. Others such as mAb against CD52 and CD20, are still under investigation; finally, the next challenge is, based on our improved understanding of the mechanisms of immune recognition and allograft rejection, to use these mAb either alone or in combination with standard immunosuppressive regimens to manipulate the allogenic response to reach antigen-specific tolerance desired in solid-organ transplantation.
    MeSH term(s) Animals ; Antibodies, Monoclonal/therapeutic use ; Antigens, CD/immunology ; Antigens, CD20/immunology ; Antigens, Neoplasm/immunology ; Antilymphocyte Serum/therapeutic use ; CD52 Antigen ; Clinical Trials as Topic ; Drug Evaluation, Preclinical ; Glycoproteins/immunology ; Graft Rejection/prevention & control ; Humans ; Immunosuppressive Agents/therapeutic use ; Interleukin-2 Receptor alpha Subunit/immunology ; Muromonab-CD3/therapeutic use ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology
    Chemical Substances Antibodies, Monoclonal ; Antigens, CD ; Antigens, CD20 ; Antigens, Neoplasm ; Antilymphocyte Serum ; CD52 Antigen ; CD52 protein, human ; Glycoproteins ; IL2RA protein, human ; Immunosuppressive Agents ; Interleukin-2 Receptor alpha Subunit ; Muromonab-CD3
    Language French
    Publishing date 2009-12
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 632733-3
    ISSN 1958-5381 ; 0767-0974
    ISSN (online) 1958-5381
    ISSN 0767-0974
    DOI 10.1051/medsci/200925121121
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  8. Article ; Online: Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687.

    Vanhove, Marc / Wagner, Jean-Marc / Noppen, Bernard / Jonckx, Bart / Vermassen, Elke / Stitt, Alan W

    Journal of pharmacokinetics and pharmacodynamics

    2021  Volume 48, Issue 6, Page(s) 837–849

    Abstract: Intravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The ... ...

    Abstract Intravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.
    MeSH term(s) Animals ; Diabetic Retinopathy/drug therapy ; Intravitreal Injections ; Macular Edema/drug therapy ; Rabbits ; Swine ; Swine, Miniature ; Vitreous Body
    Language English
    Publishing date 2021-07-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2041601-5
    ISSN 1573-8744 ; 1567-567X
    ISSN (online) 1573-8744
    ISSN 1567-567X
    DOI 10.1007/s10928-021-09774-9
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  9. Article ; Online: Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 1. THR-149.

    Vanhove, Marc / Noppen, Bernard / Wagner, Jean-Marc / Van Bergen, Tine / Barbeaux, Philippe / Stitt, Alan W

    Journal of pharmacokinetics and pharmacodynamics

    2021  Volume 48, Issue 6, Page(s) 825–836

    Abstract: Intravitreal (IVT) injection of pharmacological agents is an established and widely used procedure for the treatment of many posterior segment of the eye diseases. IVT injections permit drugs to reach high concentrations in the retina whilst limiting ... ...

    Abstract Intravitreal (IVT) injection of pharmacological agents is an established and widely used procedure for the treatment of many posterior segment of the eye diseases. IVT injections permit drugs to reach high concentrations in the retina whilst limiting systemic exposure. Beyond the risk of secondary complications such as intraocular infection, the potential of systemic adverse events cannot be neglected. Therefore, a detailed understanding of the rules governing systemic exposure following IVT drug administration remains a prerequisite for the evaluation and development of new pharmacological agents intended for eye delivery. We present here a novel mathematical model to describe and predict circulating drug levels following IVT in the rabbit eye, a species which is widely used for drug delivery, pharmacokinetic, and pharmacodynamic studies. The mathematical expression was derived from a pharmacokinetic model that assumes the existence of a compartment between the vitreous humor compartment itself and the systemic compartment. We show that the model accurately describes circulating levels of THR-149, a plasma kallikrein inhibitor in development for the treatment of diabetic macular edema. We hypothesize that the model based on the rabbit eye has broader relevance to the human eye and can be used to analyze systemic exposure of a variety of drugs delivered in the eye.
    MeSH term(s) Animals ; Diabetic Retinopathy/drug therapy ; Macular Edema/drug therapy ; Macular Edema/metabolism ; Pharmaceutical Preparations/metabolism ; Rabbits ; Retina/metabolism ; Vitreous Body/metabolism
    Chemical Substances Pharmaceutical Preparations
    Language English
    Publishing date 2021-07-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041601-5
    ISSN 1573-8744 ; 1567-567X
    ISSN (online) 1573-8744
    ISSN 1567-567X
    DOI 10.1007/s10928-021-09773-w
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  10. Article ; Online: Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells.

    Belarif, Lyssia / Vanhove, Bernard / Poirier, Nicolas

    Cell stress

    2018  Volume 2, Issue 12, Page(s) 362–364

    Abstract: Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Interleukin 7 (IL-7) is a limiting and potent cytokine produced by epithelial and stromal cells sustaining T-lymphocytes ... ...

    Abstract Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Interleukin 7 (IL-7) is a limiting and potent cytokine produced by epithelial and stromal cells sustaining T-lymphocytes development, homeostasis and cell metabolism. Almost all conventional mature T lymphocytes express the IL-7 receptor (IL-7R), with the exception for naturally-occurring regulatory T-cells (Treg), constituting a rare opportunity to selectively strangle pathogenic effectors while preserving crucial natural regulators. In our recent study, we reported that therapeutic efficacy of antagonist anti- IL-7Rα mAbs in a non-human primate model of memory T cell-induced chronic inflammation depends on recognition of an epitope overlapping the IL-7 binding domain (site 1) and the receptor heterodimerization region (site-2b) (Nat Commun, 9(1):4483). We found that "site-1-only" mAbs prevented IL-7-induced JAK/STAT signaling but induced PI3K and Erk signaling and lacked efficacy
    Language English
    Publishing date 2018-12-10
    Publishing country Austria
    Document type Journal Article ; Comment
    ISSN 2523-0204
    ISSN (online) 2523-0204
    DOI 10.15698/cst2018.12.168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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