NK cell therapy after hematopoietic stem cell transplantation: can we improve anti-tumor effect?

Elssen, Catharina H. M. J. Van; Ciurea, Stefan O.

doi:10.1007/s12185-017-2379-x

Cited by 9 publications

(5 citation statements)

References 54 publications

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“…Autologous NK cells may be inhibited by “ self ” MHC-I, thus limiting GvT effects in the absence of exogenous cytokines or antibodies ( 265 , 266 ). Therefore, allogeneic NK cells along with hematopoietic stem cell transplant has been explored as a potential treatment for patients with high-risk solid tumors ( 263 , 267 , 268 ). Using non-myeloablative conditioning regimens to provide potent immune suppression without toxicity, the burden of cure then relies on the ability of transplanted donor cells to provide a GvT effect.…”

Section: Nk Cells In Health and Diseasementioning

confidence: 99%

Natural Killer Cells: Development, Maturation, and Clinical Utilization

et al. 2018

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Natural killer (NK) cells are the predominant innate lymphocyte subsets that mediate anti-tumor and anti-viral responses, and therefore possess promising clinical utilization. NK cells do not express polymorphic clonotypic receptors and utilize inhibitory receptors (killer immunoglobulin-like receptor and Ly49) to develop, mature, and recognize “self” from “non-self.” The essential roles of common gamma cytokines such as interleukin (IL)-2, IL-7, and IL-15 in the commitment and development of NK cells are well established. However, the critical functions of pro-inflammatory cytokines IL-12, IL-18, IL-27, and IL-35 in the transcriptional-priming of NK cells are only starting to emerge. Recent studies have highlighted multiple shared characteristics between NK cells the adaptive immune lymphocytes. NK cells utilize unique signaling pathways that offer exclusive ways to genetically manipulate to improve their effector functions. Here, we summarize the recent advances made in the understanding of how NK cells develop, mature, and their potential translational use in the clinic.

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Section: Nk Cells In Health and Diseasementioning

confidence: 99%

Natural Killer Cells: Development, Maturation, and Clinical Utilization

et al. 2018

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“…Donor selection was cited as a factor in a recent Phase II study which reported good safety and no GvHD, but no significant efficacy, in patients with relapse of persistent myeloid malignancies treated with haploidentical NK cells [70]. Though most of these studies were carried out in the context of hematologic malignancies, successes with solid tumors remain limited [71].…”

Section: Allogeneic Nk Cell Immunotherapymentioning

confidence: 99%

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

Lupo

Matosevic

2019

Cancers

148

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Natural killer (NK) cells are attractive within adoptive transfer settings in cancer immunotherapy due to their potential for allogeneic use; their alloreactivity is enhanced under conditions of killer immunoglobulin-like receptor (KIR) mismatch with human leukocyte antigen (HLA) ligands on cancer cells. In addition to this, NK cells are platforms for genetic modification, and proliferate in vivo for a shorter time relative to T cells, limiting off-target activation. Current clinical studies have demonstrated the safety and efficacy of allogeneic NK cell adoptive transfer therapies as a means for treatment of hematologic malignancies and, to a lesser extent, solid tumors. However, challenges associated with sourcing allogeneic NK cells have given rise to controversy over the contribution of NK cells to graft-versus-host disease (GvHD). Specifically, blood-derived NK cell infusions contain contaminating T cells, whose activation with NK-stimulating cytokines has been known to lead to heightened release of proinflammatory cytokines and trigger the onset of GvHD in vivo. NK cells sourced from cell lines and stem cells lack contaminating T cells, but can also lack many phenotypic characteristics of mature NK cells. Here, we discuss the available published evidence for the varying roles of NK cells in GvHD and, more broadly, their use in allogeneic adoptive transfer settings to treat various cancers.

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“…There are also a number of studies estimating the combination of HSCT and NK cell transplantation. Although the efficacy remains controversial, NK cell transplantation before or after HSCT was shown to be applicable without serious side effects [ 133 , 134 , 135 ]. A phase I/II clinical trial in which AML patients received haploidentical HSCT combined with early adoptive NK cell transfer demonstrated 37% of two-year overall survival compared to 14% for patients who underwent haploindentical HSCT, suggesting that transferred NK cells may contribute to long-term remission in patients with refractory AML [ 136 ].…”

Section: Current Approaches To Nk-cell-based Immunotherapymentioning

confidence: 99%

The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors

Velichinskii

Streltsova

Erokhina

et al. 2021

IJMS

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NK cells are an attractive target for cancer immunotherapy due to their potent antitumor activity. The main advantage of using NK cells as cytotoxic effectors over T cells is a reduced risk of graft versus host disease. At present, several variants of NK-cell-based therapies are undergoing clinical trials and show considerable effectiveness for hematological tumors. In these types of cancers, the immune cells themselves often undergo malignant transformation, which determines the features of the disease. In contrast, the current use of NK cells as therapeutic agents for the treatment of solid tumors is much less promising. Most studies are at the stage of preclinical investigation, but few progress to clinical trials. Low efficiency of NK cell migration and functional activity in the tumor environment are currently considered the major barriers to NK cell anti-tumor therapies. Various therapeutic combinations, genetic engineering methods, alternative sources for obtaining NK cells, and other techniques are aiming at the development of promising NK cell anticancer therapies, regardless of tumorigenesis. In this review, we compare the role of NK cells in the pathogenesis of hematological and solid tumors and discuss current prospects of NK-cell-based therapy for hematological and solid tumors.

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NK cell therapy after hematopoietic stem cell transplantation: can we improve anti-tumor effect?

Cited by 9 publications

References 54 publications

Natural Killer Cells: Development, Maturation, and Clinical Utilization

Natural Killer Cells: Development, Maturation, and Clinical Utilization

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors

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