Scholarlink

<p>Personalized cancer vaccines (PCVs) largely leverage neoantigens arising from somatic mutations, limiting their application to patients with relatively high tumor mutational burden (TMB). This underscores the need for alternative antigens to design PCVs for low TMB cancers. To this end, we substantiate endogenous retroviral elements (EVEs) as tumor antigens through large-scale genomic analyses of healthy tissues and solid cancers. These analyses revealed that the breadth of EVE expression in tumors stratify checkpoint inhibitor-treated melanoma patients into groups with differential overall and progression-free survival. To enable the design of PCVs containing EVE-derived epitopes with therapeutic potential, we developed a computational pipeline, ObsERV. We show that EVE-derived peptides are presented as epitopes on tumors and can be predicted by ObsERV. Preclinical testing of ObsERV demonstrates induction of sustained poly-functional CD4+ and CD8+ T-cell responses as well as long-term tumor protection. As such, EVEs may facilitate and improve PCVs, especially for low-TMB patients.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Endogenous viral elements constitute a complementary source of antigens for personalized cancer vaccines

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月20日

查看全文
  • Christian Garde,
  • Michail A. Pavlidis,
  • Pablo Garces,
  • Emma J. Lange,
  • Sri H. Ramarathinam,
  • Mateo Sokač,
  • Kirti Pandey,
  • Pouya Faridi,
  • Johanne Ahrenfeldt,
  • Shanzou Chung,
  • Stine Friis,
  • Daniela Kleine-Kohlbrecher,
  • Nicolai J. Birkbak,
  • Jens V. Kringelum,
  • Birgitte Rønø,
  • Anthony W. Purcell,
  • Thomas Trolle

摘要

Personalized cancer vaccines (PCVs) largely leverage neoantigens arising from somatic mutations, limiting their application to patients with relatively high tumor mutational burden (TMB). This underscores the need for alternative antigens to design PCVs for low TMB cancers. To this end, we substantiate endogenous retroviral elements (EVEs) as tumor antigens through large-scale genomic analyses of healthy tissues and solid cancers. These analyses revealed that the breadth of EVE expression in tumors stratify checkpoint inhibitor-treated melanoma patients into groups with differential overall and progression-free survival. To enable the design of PCVs containing EVE-derived epitopes with therapeutic potential, we developed a computational pipeline, ObsERV. We show that EVE-derived peptides are presented as epitopes on tumors and can be predicted by ObsERV. Preclinical testing of ObsERV demonstrates induction of sustained poly-functional CD4+ and CD8+ T-cell responses as well as long-term tumor protection. As such, EVEs may facilitate and improve PCVs, especially for low-TMB patients.