Scholarlink

<p>In recent years, off-the-shelf cellular immunotherapies have attracted much attention as a practical alternative to autologous therapies. Within this landscape, induced pluripotent stem cell–derived natural killer cells (iPSC-derived NK cells; iPSC-NK) have emerged as a highly versatile platform because they combine renewable starting material, batch-to-batch uniformity, favorable intrinsic safety, and amenability to precise genetic engineering.This review places iPSC-NK cells within the broader field of NK cell–based immunotherapy by comparing them with peripheral blood–derived NK cells, umbilical cord blood–derived NK cells, and NK cell lines, including clinically explored NK-92–based platforms, and by outlining key distinctions between NK cell therapies and CAR-T approaches. We summarize current strategies for iPSC-to-NK differentiation, spanning feeder-based systems, feeder-free protocols, embryoid body approaches, and scalable GMP-compatible manufacturing methods. We further discuss genetic engineering strategies for NK cells, with particular emphasis on genetic tuning as a systems-level framework for coordinating CAR signaling, cytokine responsiveness, and activation–inhibition balance to improve antitumor efficacy while preserving functional stability and clinical safety. In addition, this review examines translational challenges that continue to limit broader NK-cell adoption, including incomplete functional maturation, limited persistence, donor- and source-dependent variability, manufacturing standardization, cryopreservation, and quality-control requirements. Early clinical studies of iPSC-NK products indicate a favorable safety profile and preliminary antitumor activity in selected hematologic malignancies, although durable efficacy and broader validation in solid tumors remain to be established. Importantly, iPSC-NK cells should be considered one of several complementary NK-cell platforms rather than a definitive or universally superior strategy. Overall, current evidence supports iPSC-NK cells as a promising programmable off-the-shelf platform, but their ultimate clinical impact will depend on achieving reproducible large-scale manufacturing, balanced genetic engineering, and consistent in vivo performance relative to other NK-cell sources and established CAR-T therapies.</p> Graphical Abstract <p></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

Induced Pluripotent Stem Cell–Derived NK Cells as an Off-the-Shelf Platform for Cancer Immunotherapy: Opportunities, Challenges, and Clinical Translation

  • 期刊论文

  • 发表日期：

    2026年5月26日

查看全文
  • Shiva Mosadegh Manshadi,
  • Maryam Mehravar,
  • Abbas Hajifathali,
  • Elham Roshandel,
  • Saeid Kaviani Jabali

摘要

In recent years, off-the-shelf cellular immunotherapies have attracted much attention as a practical alternative to autologous therapies. Within this landscape, induced pluripotent stem cell–derived natural killer cells (iPSC-derived NK cells; iPSC-NK) have emerged as a highly versatile platform because they combine renewable starting material, batch-to-batch uniformity, favorable intrinsic safety, and amenability to precise genetic engineering.This review places iPSC-NK cells within the broader field of NK cell–based immunotherapy by comparing them with peripheral blood–derived NK cells, umbilical cord blood–derived NK cells, and NK cell lines, including clinically explored NK-92–based platforms, and by outlining key distinctions between NK cell therapies and CAR-T approaches. We summarize current strategies for iPSC-to-NK differentiation, spanning feeder-based systems, feeder-free protocols, embryoid body approaches, and scalable GMP-compatible manufacturing methods. We further discuss genetic engineering strategies for NK cells, with particular emphasis on genetic tuning as a systems-level framework for coordinating CAR signaling, cytokine responsiveness, and activation–inhibition balance to improve antitumor efficacy while preserving functional stability and clinical safety. In addition, this review examines translational challenges that continue to limit broader NK-cell adoption, including incomplete functional maturation, limited persistence, donor- and source-dependent variability, manufacturing standardization, cryopreservation, and quality-control requirements. Early clinical studies of iPSC-NK products indicate a favorable safety profile and preliminary antitumor activity in selected hematologic malignancies, although durable efficacy and broader validation in solid tumors remain to be established. Importantly, iPSC-NK cells should be considered one of several complementary NK-cell platforms rather than a definitive or universally superior strategy. Overall, current evidence supports iPSC-NK cells as a promising programmable off-the-shelf platform, but their ultimate clinical impact will depend on achieving reproducible large-scale manufacturing, balanced genetic engineering, and consistent in vivo performance relative to other NK-cell sources and established CAR-T therapies.

Graphical Abstract