Donor selection based on NK alloreactivity for patients with hematological malignancies

Zhang, Qiuheng Jennifer

doi:10.1016/j.humimm.2022.07.006

Cited by 7 publications

(7 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of HCT and GVL, donor derived NK cells may identify leukemic cells that have downregulated or lack cognate HLA class I molecules to donor iKIRs ( 35 – 38 ) or those with surface markers that interact with NK cell activation receptors ( 18 ). After activation, NK cells conduct cell-killing through either release of cytotoxic granules loaded with perforin and granzymes, leading to target cell lysis, or through induction of Fas-L- or TRAIL- mediated target cell lysis ( 27 , 38 ). NK cells also secrete pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6), which contribute to both innate and adaptive immunity in the GVL reaction ( 38 ).…”

Section: Nk Cell Biology and Role In The Graft-versus-leukemia Effectmentioning

confidence: 99%

“…After activation, NK cells conduct cell-killing through either release of cytotoxic granules loaded with perforin and granzymes, leading to target cell lysis, or through induction of Fas-L- or TRAIL- mediated target cell lysis ( 27 , 38 ). NK cells also secrete pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6), which contribute to both innate and adaptive immunity in the GVL reaction ( 38 ).…”

Section: Nk Cell Biology and Role In The Graft-versus-leukemia Effectmentioning

confidence: 99%

See 1 more Smart Citation

The role and novel use of natural killer cells in graft-versus-leukemia reactions after allogeneic transplantation

Hadjis,

McCurdy

2024

Front. Immunol.

View full text Add to dashboard Cite

Allogeneic hematopoietic cell transplantation (HCT) has transformed over the past several decades through enhanced supportive care, reduced intensity conditioning (RIC), improved human leukocyte antigen (HLA) typing, and novel graft-versus-host disease (GVHD)-prevention and treatment strategies. Most notably, the implementation of post-transplantation cyclophosphamide (PTCy) has dramatically increased the safety and availability of this life-saving therapy. Given reductions in nonrelapse mortality (NRM) with these advances, the HCT community has placed even greater emphasis on developing ways to reduce relapse - the leading cause of death after HCT. When using RIC HCT, protection from relapse relies predominantly on graft-versus-leukemia (GVL) reactions. Donor lymphocyte infusion (DLI), adoptive cellular therapy, checkpoint inhibition, and post-HCT maintenance strategies represent approaches under study that aim to augment or synergize with the GVL effects of HCT. Optimizing donor selection algorithms to leverage GVL represents another active area of research. Many of these strategies seek to harness the effects of T cells, which for decades were felt to be the primary mediators of GVL and the focus of investigation in relapse reduction. However, there is growing interest in capitalizing on the ability of natural killer (NK) cells to yield potent anti-tumor effects. A potential advantage of NK cell-based approaches over T cell-mediated is the potential to reduce NRM in addition to relapse. By decreasing infection, without increasing the risk of GVHD, NK cells may mitigate NRM, while still yielding relapse reduction through identification and clearance of cancer cells. Most T cell-focused relapse-prevention strategies must weigh the benefits of relapse reduction against the increased risk of NRM from GVHD. In contrast, NK cells have the potential to reduce both, potentially tipping the scales significantly in favor of survival. Here, we will review the role of NK cells in GVL, optimization of NK cell match or mismatch, and burgeoning areas of research in NK cell therapy such as adoptive transfer and chimeric antigen receptor (CAR) NK cells.

show abstract

Section: Nk Cell Biology and Role In The Graft-versus-leukemia Effectmentioning

confidence: 99%

Section: Nk Cell Biology and Role In The Graft-versus-leukemia Effectmentioning

confidence: 99%

The role and novel use of natural killer cells in graft-versus-leukemia reactions after allogeneic transplantation

Hadjis,

McCurdy

2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Despite the success of adoptive NK cell therapy, immune cell depletion remains a therapeutic barrier. To develop the next generation of CAR-NK cells, the negative regulator of NK cells may be a potential new design direction ( 96 – 98 ). T cell immune checkpoints affect CAR-T cell therapy.…”

Section: Car-nk Cell and Immune Checkpoint Therapiesmentioning

confidence: 99%

“…To develop the next generation of CAR-NK cells, the identification of negative regulators of NK cell immune functions is required. Some checkpoint receptors, such as PD-1, LAG-3, TIM-3, TIGIT, and killer cell lectin-like receptor subfamily G member 1 (KLRG1), are upregulated in exhausted NK cells ( 96 , 98 ). NKG2A is one of the most prominent inhibitory NK cell receptors, and its gene deletion is associated with increased NK cell cytotoxicity against tumors ( 117 ).…”

Section: Combination Of Car-nk Cells Therapy and Immune Checkpoint Th...mentioning

confidence: 99%

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Yang

Zhao²,

Sun³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is an attractive research field in tumor immunotherapy. While CAR is genetically engineered to express certain molecules, it retains the intrinsic ability to recognize tumor cells through its own receptors. Additionally, NK cells do not depend on T cell receptors for cytotoxic killing. CAR-NK cells exhibit some differences to CAR-T cells in terms of more precise killing, numerous cell sources, and increased effectiveness in solid tumors. However, some problems still exist with CAR-NK cell therapy, such as cytotoxicity, low transfection efficiency, and storage issues. Immune checkpoints inhibit immune cells from performing their normal killing function, and the clinical application of immune checkpoint inhibitors for cancer treatment has become a key therapeutic strategy. The application of CAR-T cells and immune checkpoint inhibitors is being evaluated in numerous ongoing basic research and clinical studies. Immune checkpoints may affect the function of CAR-NK cell therapy. In this review, we describe the combination of existing CAR-NK cell technology with immune checkpoint therapy and discuss the research of CAR-NK cell technology and future clinical treatments. We also summarize the progress of clinical trials of CAR-NK cells and immune checkpoint therapy.

show abstract

“…The effects of natural killer (NK) cell alloreactivity on disease relapse and transplant-related mortality following allogeneic stem cell transplantation have been recognized over the past decades ( Jennifer Zhang, 2022 ). Killer immunoglobin-like receptors (KIRs), which recognize HLA class I molecules, are the key receptors in regulating NK cell functions.…”

Section: Introductionmentioning

confidence: 99%

Advancing precision in histocompatibility and immunogenetics: a comprehensive review of the UCLA exchange program

Zhang,

Locke,

Alvarez

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

Precise typing of human leukocyte antigens (HLA) is crucial for clinical hematopoietic stem cell and solid organ transplantations, transfusion medicine, HLA-related disease association, and drug hypersensitivity analysis. The UCLA Cell Exchange program has played a vital role in providing educational and proficiency testing surveys to HLA laboratories worldwide for the past 5 decades. This article highlights the significant contribution of the UCLA Cell and DNA Exchange Programs in advancing HLA antibody testing, genotyping, crossmatches, and, more recently, virtual crossmatches. Additionally, we discuss future directions of the UCLA Cell Exchange program to support histocompatibility testing to adapt to the fast-evolving field of immunotherapy, tolerance and xenotransplantation.

show abstract

Donor selection based on NK alloreactivity for patients with hematological malignancies

Cited by 7 publications

References 94 publications

The role and novel use of natural killer cells in graft-versus-leukemia reactions after allogeneic transplantation

The role and novel use of natural killer cells in graft-versus-leukemia reactions after allogeneic transplantation

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Advancing precision in histocompatibility and immunogenetics: a comprehensive review of the UCLA exchange program

Contact Info

Product

Resources

About