内源性逆转录病毒
免疫原性
逆转录病毒
病毒学
抗原
接种疫苗
生物
癌症研究
疫苗效力
病毒
医学
基因组
免疫学
基因
遗传学
作者
Joana Daradoumis,Emeline Ragonnaud,Isabella Skandorff,Karen Nørgaard Nielsen,Amaia Vergara Bermejo,Anne‐Marie Andersson,Silke Schrödel,Christian Thirion,Lasse Neukirch,Peter Johannes Holst
出处
期刊:Viruses
[MDPI AG]
日期:2023-04-06
卷期号:15 (4): 926-926
被引量:4
摘要
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.
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