دورية أكاديمية
أعرض في EDS

First-in-human Study With LIS1, a Next-generation Porcine Low Immunogenicity Antilymphocyte Immunoglobulin in Kidney Transplantation.

التفاصيل البيبلوغرافية
العنوان: First-in-human Study With LIS1, a Next-generation Porcine Low Immunogenicity Antilymphocyte Immunoglobulin in Kidney Transplantation.
المؤلفون: Viklicky O; Department of Nephrology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic., Slatinska J; Department of Nephrology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic., Janousek L; Department of Nephrology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic., Rousse J; Xenothera, Nantes, France., Royer PJ; Xenothera, Nantes, France., Toutain PL; Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom.; INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France., Cozzi E; Transplantation Immunology Unit, Padua University Hospital, Padova, Italy., Galli C; Avantea, Laboratory of Reproductive Technologies, Cremona, Italy., Evanno G; Xenothera, Nantes, France., Duvaux O; Xenothera, Nantes, France., Bach JM; Oniris, INRAE, IECM, USC 1383, Nantes, France., Soulillou JP; Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.; Nantes Université, INSERM UMR1064, Center for Research in Transplantation and Translational Immunology, Nantes, France., Giral M; Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.; Nantes Université, INSERM UMR1064, Center for Research in Transplantation and Translational Immunology, Nantes, France., Vanhove B; Xenothera, Nantes, France., Blancho G; Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.; Nantes Université, INSERM UMR1064, Center for Research in Transplantation and Translational Immunology, Nantes, France.
المصدر: Transplantation [Transplantation] 2024 Jul 01; Vol. 108 (7), pp. e139-e147. Date of Electronic Publication: 2024 Feb 29.
نوع المنشور: Journal Article; Clinical Trial, Phase I
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0132144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1534-6080 (Electronic) Linking ISSN: 00411337 NLM ISO Abbreviation: Transplantation Subsets: MEDLINE
أسماء مطبوعة: Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Williams & Wilkins.
مواضيع طبية MeSH: Kidney Transplantation*/adverse effects , Antilymphocyte Serum*/immunology, Humans ; Animals ; Male ; Middle Aged ; Swine ; Female ; Adult ; T-Lymphocytes/immunology ; T-Lymphocytes/drug effects ; Lymphocyte Depletion/methods ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/therapeutic use ; Treatment Outcome ; Galactosyltransferases
مستخلص: 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/mm 3 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.
Competing Interests: J.R., P.-J.R., G.E., O.D., and B.V. are employees of Xenothera. O.D., J.-P.S., J.-M.B., and C.G. are cofounders of Xenothera. The other authors declare no conflicts of interest.
(Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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سلسلة جزيئية: ClinicalTrials.gov NCT04431219
المشرفين على المادة: 0 (Antilymphocyte Serum)
0 (Immunosuppressive Agents)
EC 2.4.1.- (alpha-1,3-galactosyltransferase 1, porcine)
EC 2.4.1.- (Galactosyltransferases)
تواريخ الأحداث: Date Created: 20240710 Date Completed: 20240710 Latest Revision: 20240710
رمز التحديث: 20240711
DOI: 10.1097/TP.0000000000004967
PMID: 38985979
قاعدة البيانات: MEDLINE
الوصف
تدمد:1534-6080
DOI:10.1097/TP.0000000000004967