A replicating LCMV-based vaccine for the treatment of solid tumors.

adoptive cell transfer cancer immunotherapy melanoma self-antigens viral-vector-based vaccines

Journal

Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581

Informations de publication

Date de publication:
05 Dec 2023
Historique:
received: 17 04 2023
revised: 31 10 2023
accepted: 30 11 2023
pubmed: 7 12 2023
medline: 7 12 2023
entrez: 7 12 2023
Statut: aheadofprint

Résumé

Harnessing the immune system to eradicate tumors requires identification and targeting of tumor antigens, including tumor-specific neoantigens and tumor-associated self-antigens. Tumor-associated antigens are subject to existing immune tolerance, which must be overcome by immunotherapies. Despite many novel immunotherapies reaching clinical trials, inducing self-antigen-specific immune responses remains challenging. Here, we systematically investigate viral-vector-based cancer vaccines encoding a tumor-associated self-antigen (TRP2) for the treatment of established melanomas in preclinical mouse models, alone or in combination with adoptive T cell therapy. We reveal that, unlike foreign antigens, tumor-associated antigens require replication of lymphocytic choriomeningitis virus (LCMV)-based vectors to break tolerance and induce effective antigen-specific CD8

Identifiants

pubmed: 38058126
pii: S1525-0016(23)00659-7
doi: 10.1016/j.ymthe.2023.11.026
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests C.M.S. is a scientific advisor to, has stock options in, and has received research funding from Enable Medicine, Inc. L.F. is a founder and shareholder of Hookipa Pharma Inc. F.S., S.S., and K.K.O. are employees and stock option holder of Hookipa Pharma, Inc. L.F., S.S.R., S.S., and K.K.O. are listed as inventors of the patent entitled “Arenavirus particles to treat solid tumors” (patent number WO2018/185307 A1) describing the application of artLCMV vectors in the treatment of tumors.

Auteurs

Mette-Triin Purde (MT)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Jovana Cupovic (J)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Yannick A Palmowski (YA)

Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany.

Ahmad Makky (A)

Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany.

Sarah Schmidt (S)

Hookipa Pharma Inc., New York, NY 10118, USA.

Alexander Rochwarger (A)

Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany.

Fabienne Hartmann (F)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Felix Stemeseder (F)

Hookipa Pharma Inc., New York, NY 10118, USA.

Alexander Lercher (A)

Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, 1090 Vienna, Austria.

Marie-Therese Abdou (MT)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

David Bomze (D)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Lenka Besse (L)

Laboratory of Experimental Oncology, Department of Oncology and Hematology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Fiamma Berner (F)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Thomas Tüting (T)

Laboratory of Experimental Dermatology, Department of Dermatology, University Hospital Magdeburg, 39120 Magdeburg, Germany.

Michael Hölzel (M)

Institute of Experimental Oncology, University Hospital Bonn, 53127 Bonn, Germany.

Andreas Bergthaler (A)

Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, 1090 Vienna, Austria.

Stefan Kochanek (S)

Department of Gene Therapy, Ulm University, 89081 Ulm, Germany.

Burkhard Ludewig (B)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Henning Lauterbach (H)

Hookipa Pharma Inc., New York, NY 10118, USA.

Klaus K Orlinger (KK)

Hookipa Pharma Inc., New York, NY 10118, USA.

Tobias Bald (T)

QIMR Medical Research Institute, Herston, QLD 4006, Australia.

Andrea Schietinger (A)

Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Christian Schürch (C)

Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany.

Sandra S Ring (SS)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.

Lukas Flatz (L)

Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland; Department of Dermatology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland. Electronic address: lukas.flatz@med.uni-tuebingen.de.

Classifications MeSH