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<p>Neoantigen-based adoptive T cell therapies (ACTs) represent a promising avenue in cancer immunotherapy due to their exquisite tumor specificity. The first cell-based immunotherapy for a solid tumor, comprising tumor-infiltrating lymphocytes, recently received FDA approval. Building on this, we designed a distinct ACT approach, where T cell responses against personalized neoantigens are systematically generated from autologous peripheral blood. Here we report the establishment of NEO-STIM, an ex vivo induction process to prime and expand pre-existing memory and de novo CD8<sup>+</sup> and CD4<sup>+</sup> T cell responses, thereby highlighting critical parameters for generating potent neoantigen-specific T cell responses. The drug products comprise mutant-reactive, polyfunctional, and cytotoxic CD8<sup>+</sup> and CD4<sup>+</sup> T cells, able to recognize autologous tumor material. Following infusion, T cell responses are detected in tumor and blood of a patient, and display activated/exhausted and cytotoxic phenotypes. A first-in-human clinical trial (NCT04625205) recently further validated proof-of-concept, supporting continued development of this ACT approach.</p>

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NEO-STIM advances personalized neoantigen-specific adoptive T cell therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月5日

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  • Divya Lenkala,
  • Jessica Kohler,
  • Brian McCarthy,
  • Michael Nelson,
  • Noor A. M. Bakker,
  • Renate de Boer,
  • Emily K. Jackson,
  • Joong Hyuk F. Sheen,
  • Susan Hannes,
  • Ekaterina Esaulova,
  • Kai Stewart,
  • Claudia Gottstein,
  • John Attanasio,
  • Flavian D. Brown,
  • Sebastian Hymson,
  • Shirisha Meda,
  • Maaike van Zon,
  • Saskia Scheij,
  • Rhianne Voogd,
  • Brenda Raud,
  • Ziyan Xu,
  • Jessica S. W. Borgers,
  • Maartje W. Rohaan,
  • Kristen N. Balogh,
  • Asaf Poran,
  • Michael Rooney,
  • Jesse Z. Dong,
  • John R. Srouji,
  • Vikram R. Juneja,
  • Christina M. Arieta,
  • Cynthia M. Nijenhuis,
  • Bastiaan Nuijen,
  • Mark DeMario,
  • Kelledy Manson,
  • Ton N. M. Schumacher,
  • Richard B. Gaynor,
  • John B. Haanen,
  • Joost H. van den Berg,
  • Marit M. van Buuren

摘要

Neoantigen-based adoptive T cell therapies (ACTs) represent a promising avenue in cancer immunotherapy due to their exquisite tumor specificity. The first cell-based immunotherapy for a solid tumor, comprising tumor-infiltrating lymphocytes, recently received FDA approval. Building on this, we designed a distinct ACT approach, where T cell responses against personalized neoantigens are systematically generated from autologous peripheral blood. Here we report the establishment of NEO-STIM, an ex vivo induction process to prime and expand pre-existing memory and de novo CD8+ and CD4+ T cell responses, thereby highlighting critical parameters for generating potent neoantigen-specific T cell responses. The drug products comprise mutant-reactive, polyfunctional, and cytotoxic CD8+ and CD4+ T cells, able to recognize autologous tumor material. Following infusion, T cell responses are detected in tumor and blood of a patient, and display activated/exhausted and cytotoxic phenotypes. A first-in-human clinical trial (NCT04625205) recently further validated proof-of-concept, supporting continued development of this ACT approach.