The rise of human stem cell-derived natural killer cells for cancer immunotherapy

ABSTRACT

Introduction: Natural killer (NK) cell therapy has been proven to be safe and clinically effective for the treatment of multiple cancers, in particular blood cancers. Most of the clinical trials use primary NK cells from peripheral blood or umbilical cord blood, or NK-92 cells. Each cell source is confined by limitations, such as donor dependence, low persistence in vivo, and its difficulty to genetically modify. Thus, there is an urgent need to explore novel NK cell sources for clinical use.

Areas covered: This article highlights the recent progress in utilizing stem cell-derived NK cells as anticancer therapies and strategies to improve their antitumor activities.

Expert commentary: Stem cell-derived NK cells are homogenous, easy to genetically modify on a clonal level, and can be expanded to clinical scale. They may therefore arise as an ideal population for developing off-the-shelf, standardized adoptive NK cell therapeutic products.

KEYWORDS:

• Human stem cells
• natural killer cells
• cancer immunotherapy
• chimeric antigen receptor
• CAR NK

Article highlights

• NK cell therapy has been shown to be safe and effective clinically for the treatment of some cancers, in particular blood cancers.

• NK cells might be routinely derived from human stem cells at clinical scale with technology advance.

• Human stem cell-derived NK cells are arising as an ideal population for developing off-the-shelf, standardized adoptive NK cell therapeutic products.

• Strategies to improve the antitumor function of NK cells include increasing antitumor activity and specificity via CAR modification, improving in vivo persistence, and enhancing ADCC functions.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.