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NK Cells and γδT Cells for Relapse Protection after Allogeneic Hematopoietic Cell Transplantation (HCT)

  • Cellular Therapies: Preclinical and Clinical (EM Horwitz, Section Editor)
  • Published:
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Abstract

Purpose of Review

The outcome of allogeneic stem cell transplantation (allo-HCT) is still compromised by relapse and complications. NK cells and γδT cells, effectors that both function through MHC-unrestricted mechanisms, can target transformed and infected cells without inducing graft-versus-host disease (GVHD). Allo-HCT platforms based on CD34+ selection or αβ-TCR depletion result in low grades of GVHD, early immune reconstitution (IR) of NK and γδT cells and minimal usage of GVHD prophylaxis. In this review we will discuss strategies to retain and expand the quantity, diversity, and functionality of these reconstituting innate cell types.

Recent Findings

Bisphosphonates, IL-15 cytokine administration, specific antibodies, checkpoint inhibitors, and (CMV based) vaccination are currently being evaluated to enhance IR. All these approaches have shown to potentially enhance both NK and γδT cell immuno-repertoires.

Summary

Rapidly accumulating data linking innate biology to proposed clinical immune interventions will give unique opportunities to unravel shared pathways which determine the graft-versus-tumor effects of NK and γδT cells.

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Acknowledgments

Moniek A. de Witte received the following funding: KWF UU 2015-7553. Jeffrey S. Miller received the following funding: NIH/NCI P01 CA65493, NIH/NCI P01 CA111412, NIH/NCI R35 CA197292. Funding for this study was provided by ZonMW 43400003 and VIDI-ZonMW 917.11.337, KWF UU 2010-4669, UU 2013-6426, UU 2014-6790 and UU 2015-7601, Vrienden van het UMCU, AICR 10-0736 & 15-0049 to J.K.

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Authors and Affiliations

  1. Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA

    Moniek A. de Witte & Jeffrey S. Miller

  2. Department of Hematology, Cancer Center, University Medical Centre Utrecht, Utrecht, The Netherlands

    Moniek A. de Witte & Jürgen Kuball

  3. Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands

    Jürgen Kuball

  4. Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA

    Jeffrey S. Miller

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  1. Moniek A. de Witte
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Correspondence to Jeffrey S. Miller.

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Conflict of Interest

Moniek A. de Witte has no conflict of interest.

Jürgen Kuball is scientific co-founder and CSO of Gadeta BV (www.gadeta.nl) and is a shareholder. He is also an inventor on different patents given to Gadeta via the University Medical Centre Utrecht that deal with γδ TCR, processing strategies, and their ligands. In addition, he has received grants from Novartis and Miltenyi Biotech.

Jeffrey S. Miller is a consultant and scientific advisory for Fate Therapeutics and GT Biopharma. He also is on the scientific advisory board for Celgene. In addition, he has pending patents via the University of Minnesota for Fate Therapeutics and GT Biopharma.

Human and Animal Rights and Informed Consent

This article refers to published studies with both human and animal subjects performed by the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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This article is part of the Topical Collection on Cellular Therapies: Preclinical and Clinical

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de Witte, M.A., Kuball, J. & Miller, J.S. NK Cells and γδT Cells for Relapse Protection after Allogeneic Hematopoietic Cell Transplantation (HCT). Curr Stem Cell Rep 3, 301–311 (2017). https://doi.org/10.1007/s40778-017-0106-4

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