Potential of NK cells in multiple Myeloma therapy

ABSTRACT

Introduction: Despite rapid advances in myeloma treatment with the development of new drugs, curative therapies remain elusive. Relapsed/refractory disease related to progressive dysregulation of immune system and acquired genetic abnormalities continues to be a major obstacle in achieving cure. Immune-based therapy harnessing the host defense mechanism of natural killer (NK) cells is a promising avenue in the treatment of myeloma.

Areas covered: Here, we discuss the biology and cytotoxic activity of NK cells and the potential role of these innate immune cells in defense against cancer and specifically multiple myeloma. We also discuss the role of NK cells in the anti-myeloma effects of autologous and allogeneic stem cell transplantation, various novel drugs, and treatment modalities such as chimeric antigen receptor therapy. Immune evasion, either directly or indirectly involving NK cell dysfunction, may be a key and under-recognized mechanism in myeloma progression. We reviewed extensive literature identified using the keywords immunotherapy, natural killer cells, and multiple myeloma.

Expert opinion: Novel treatment approaches in myeloma utilizing the immunomodulatory and cytotoxic properties of NK cells to eradicate resistant and quiescent clones could pave the way for potentially curative interventions.

KEYWORDS:

• Immunotherapy
• innate immunity
• monoclonal gammopathy of undetermined significance
• multiple myeloma
• natural killer cells

Article Highlights

• Natural killer (NK) cells are large granular lymphocytes of the innate immune system that play a key role in immune surveillance and eradication of virally infected and malignantly transformed cells.

• NK cells survey, acquire, and lyse targets through means complementary to adoptive immunity.

• Myeloma exerts immunoevasive strategies to impair the NK cell immune response.

• Many currently available therapies exert anti-myeloma effects, in part, through modulation of the NK cell versus myeloma axis.

• Future research to deepen understanding of the reciprocal immune editing between NK cells and myeloma cells may be critical to furthering the development of novel immunotherapies.

Acknowledgments

The authors thank Dr. David M. Lucas for his review of the manuscript.

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.