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

Autor:	Purde MT; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Cupovic J; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Palmowski YA; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany., Makky A; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany., Schmidt S; Hookipa Pharma Inc., New York, NY 10118, USA., Rochwarger A; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany., Hartmann F; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Stemeseder F; Hookipa Pharma Inc., New York, NY 10118, USA., Lercher A; Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, 1090 Vienna, Austria., Abdou MT; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Bomze D; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Besse L; Laboratory of Experimental Oncology, Department of Oncology and Hematology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Berner F; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Tüting T; Laboratory of Experimental Dermatology, Department of Dermatology, University Hospital Magdeburg, 39120 Magdeburg, Germany., Hölzel M; Institute of Experimental Oncology, University Hospital Bonn, 53127 Bonn, Germany., Bergthaler A; Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, 1090 Vienna, Austria., Kochanek S; Department of Gene Therapy, Ulm University, 89081 Ulm, Germany., Ludewig B; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., Lauterbach H; Hookipa Pharma Inc., New York, NY 10118, USA., Orlinger KK; Hookipa Pharma Inc., New York, NY 10118, USA., Bald T; QIMR Medical Research Institute, Herston, QLD 4006, Australia., Schietinger A; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Schürch C; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72076 Tübingen, Germany., Ring SS; Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland., 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.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2024 Feb 07; Vol. 32 (2), pp. 426-439. Date of Electronic Publication: 2023 Dec 05.
DOI:	10.1016/j.ymthe.2023.11.026
Abstrakt:	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 + T cell responses. Immunization with a replicating LCMV vector leads to complete tumor rejection when combined with adoptive TRP2-specific T cell transfer. Importantly, immunization with replicating vectors leads to extended antigen persistence in secondary lymphoid organs, resulting in efficient T cell priming, which renders previously "cold" tumors open to immune infiltration and reprograms the tumor microenvironment to "hot." Our findings have important implications for the design of next-generation immunotherapies targeting solid cancers utilizing viral vectors and adoptive cell transfer. Competing Interests: 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. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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