An Endogenous Retrovirus Vaccine Encoding an Envelope with a Mutated Immunosuppressive Domain in Combination with Anti-PD1 Treatment Eradicates Established Tumours in Mice.

Autor: Daradoumis J; Department of Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark., Ragonnaud E; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark.; Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark., Skandorff I; Department of Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark., Nielsen KN; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark., Bermejo AV; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark.; Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark., Andersson AM; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark., Schroedel S; Sirion Biotech GmbH, 82166 Graefelfing, Germany., Thirion C; Sirion Biotech GmbH, 82166 Graefelfing, Germany., Neukirch L; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark.; Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark., Holst PJ; Department of Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.; InProTher, Bioinnovation Institute, COBIS, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2023 Apr 06; Vol. 15 (4). Date of Electronic Publication: 2023 Apr 06.
DOI: 10.3390/v15040926
Abstrakt: Endogenous retroviruses (ERVs) account for 8% of our genome, and, although they are usually silent in healthy tissues, they become reactivated and expressed in pathological conditions such as cancer. Several studies support a functional role of ERVs in tumour development and progression, specifically through their envelope (Env) protein, which contains a region described as an immunosuppressive domain (ISD). We have previously shown that targeting of the murine ERV (MelARV) Env using virus-like vaccine (VLV) technology, consisting of an adenoviral vector encoding virus-like particles (VLPs), induces protection against small tumours in mice. Here, we investigate the potency and efficacy of a novel MelARV VLV with a mutated ISD (ISDmut) that can modify the properties of the adenoviral vaccine-encoded Env protein. We show that the modification of the vaccine's ISD significantly enhanced T-cell immunogenicity in both prime and prime-boost vaccination regimens. The modified VLV in combination with an α-PD1 checkpoint inhibitor (CPI) exhibited excellent curative efficacy against large established colorectal CT26 tumours in mice. Furthermore, only ISDmut-vaccinated mice that survived CT26 challenge were additionally protected against rechallenge with a triple-negative breast cancer cell line (4T1), showing that our modified VLV provides cross-protection against different tumour types expressing ERV-derived antigens. We envision that translating these findings and technology into human ERVs (HERVs) could provide new treatment opportunities for cancer patients with unmet medical needs.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje