TY - JOUR
T1 - NK cell therapy for hematologic malignancies
AU - Mehta, Rohtesh S.
AU - Randolph, Brion
AU - Daher, May
AU - Rezvani, Katayoun
N1 - Publisher Copyright:
© 2018, The Japanese Society of Hematology.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Natural killer (NK) cells are part of the innate immune system and represent the first line of defense against infections and tumors. In contrast to T cells, NK cells do not require prior antigen sensitization to induce cytotoxicity and do not cause graft-versus-host disease. These, along with other advantages, make NK cells an attractive candidate for adoptive cellular therapy. Herein, we describe the mechanisms of NK cell cytotoxicity, which is governed by an intricate balance between various activating and inhibitory receptors, including the killer cell immunoglobulin-like receptors (KIRs). We illustrate the advantages of NK alloreactivity as demonstrated in various types of hematopoietic stem cell transplants (HSCT), such as haploidentical, human leukocyte antigen-matched related or unrelated donor and umbilical cord blood transplant. We elaborate on different models used to predict NK cell alloreactivity in these studies, which are either based on the absence of the ligands for inhibitory KIRs, presence of activating NK cell receptors and KIR genes content in donors, or a combination of these. We will review clinical studies demonstrating anti-tumor efficacy of NK cells used either as a stand-alone immunotherapy or as an adjunct to HSCT and novel genetic engineering strategies to improve the anti-tumor activity of NK cells.
AB - Natural killer (NK) cells are part of the innate immune system and represent the first line of defense against infections and tumors. In contrast to T cells, NK cells do not require prior antigen sensitization to induce cytotoxicity and do not cause graft-versus-host disease. These, along with other advantages, make NK cells an attractive candidate for adoptive cellular therapy. Herein, we describe the mechanisms of NK cell cytotoxicity, which is governed by an intricate balance between various activating and inhibitory receptors, including the killer cell immunoglobulin-like receptors (KIRs). We illustrate the advantages of NK alloreactivity as demonstrated in various types of hematopoietic stem cell transplants (HSCT), such as haploidentical, human leukocyte antigen-matched related or unrelated donor and umbilical cord blood transplant. We elaborate on different models used to predict NK cell alloreactivity in these studies, which are either based on the absence of the ligands for inhibitory KIRs, presence of activating NK cell receptors and KIR genes content in donors, or a combination of these. We will review clinical studies demonstrating anti-tumor efficacy of NK cells used either as a stand-alone immunotherapy or as an adjunct to HSCT and novel genetic engineering strategies to improve the anti-tumor activity of NK cells.
KW - Adoptive immunotherapy
KW - Cord blood
KW - HLA mismatch
KW - Haploidentical
KW - Hematopoietic stem cell transplant
KW - Immunotherapy
KW - KIR
KW - KIR mismatch
KW - NK cells
KW - Natural killer cells
KW - Stem cell transplant
UR - http://www.scopus.com/inward/record.url?scp=85041216059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041216059&partnerID=8YFLogxK
U2 - 10.1007/s12185-018-2407-5
DO - 10.1007/s12185-018-2407-5
M3 - Review article
C2 - 29383623
AN - SCOPUS:85041216059
SN - 0925-5710
VL - 107
SP - 262
EP - 270
JO - International journal of hematology
JF - International journal of hematology
IS - 3
ER -