دورية أكاديمية
أعرض في EDS

Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis.

التفاصيل البيبلوغرافية
العنوان: Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis.
المؤلفون: Bella Á; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Arrizabalaga L; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Di Trani CA; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Gonzalez-Gomariz J; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Gomar C; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Russo-Cabrera JS; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Olivera I; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Cirella A; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Fernandez-Sendin M; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Alvarez M; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Teijeira A; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain., Atay C; Bavarian Nordic GmbH, Martinsried, Germany., Medina-Echeverz J; Bavarian Nordic GmbH, Martinsried, Germany., Hinterberger M; Bavarian Nordic GmbH, Martinsried, Germany., Hochrein H; Bavarian Nordic GmbH, Martinsried, Germany., Melero I; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Department of Oncology and Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, Pamplona, Spain.; Nuffield Department of Medicine and Oxford Center for Immuno-Oncology, University of Oxford, Oxford, UK., Berraondo P; Navarra Institute for Health Research (IDISNA), Pamplona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Aranda F; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain faranda@unav.es.; Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Nov; Vol. 11 (11).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مواضيع طبية MeSH: Interleukin-12*/genetics , Peritoneal Neoplasms*, Animals ; Mice ; Omentum ; Vaccinia virus/genetics ; Luciferases
مستخلص: Background: Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.
Methods: MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.
Results: Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8 + T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.
Conclusion: Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity.
Competing Interests: Competing interests: IM reports advisory roles with Roche-Genentech, Bristol-Myers Squibb, CYTOMX, Incyte, MedImmune, Tusk, F-Star, Genmab, Molecular Partners, Alligator, Bioncotech, MSD, Merck Serono, Boehringer Ingelheim, AstraZeneca, Numab, Catalym, and Bayer, and research funding from Roche, BMS, Alligator, and Highlight Therapeutics. PB and FA received research funding from Bavarian Nordic. CA, JM-E (former), MH, and HH are employees of Bavarian Nordic. The rest of the authors have no conflict of interest to declare.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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فهرسة مساهمة: Keywords: Cytokines; Lymphocyte Activation; Translational Medical Research; Tumor Microenvironment; Vaccination
المشرفين على المادة: 187348-17-0 (Interleukin-12)
EC 1.13.12.- (Luciferases)
SCR Organism: Modified Vaccinia Ankara virus
تواريخ الأحداث: Date Created: 20231102 Date Completed: 20231106 Latest Revision: 20240105
رمز التحديث: 20240105
مُعرف محوري في PubMed: PMC10626836
DOI: 10.1136/jitc-2023-006702
PMID: 37918917
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1136/jitc-2023-006702