Donor Killer Immunoglobulin-Like Receptor Profile Bx1 Imparts a Negative Effect and Centromeric B-Specific Gene Motifs Render a Positive Effect on Standard-Risk Acute Myeloid Leukemia/Myelodysplastic Syndrome Patient Survival after Unrelated Donor Hematopoietic Stem Cell Transplantation

Bao, Xiaojing; Wang, Miao; Zhou, Huifen; Zhang, Huanhuan; Wu, Xiaojin; Yuan, Xin; Li, Yang; Wu, Depei; He, Jun

doi:10.1016/j.bbmt.2015.09.007

Cited by 15 publications

(14 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A follow-up study on 1409 UD transplants for AML and ALL concluded that the total centromeric and telomeric B content was the best predictor of success but also confirmed the major importance of cen-B motifs and, in particular, the presence of KIR2DS2/2DL2 [18]. Furthermore, a Chinese study of 210 UD transplants likewise demonstrated the critical importance of KIR2DS2/2DL2 in the survival benefit seen with B/x donors [41]. It is of interest that KIR2DS2 has no detectable avidity to class I HLA [42,43] and that its ligand(s) remains unclear.…”

Section: Discussionmentioning

confidence: 90%

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

Solomon

Aubrey²,

Zhang

et al. 2018

Biology of Blood and Marrow Transplantation

101

View full text Add to dashboard Cite

The use of post-transplant cyclophosphamide (PTCy)-based haploidentical (haplo) transplant is increasing worldwide. However, because multiple potential haplo donors are usually available, data-driven guidance is clearly needed to help transplant centers prioritize donors. To that end, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving PTCy-based haplo transplant at a single institution. Median recipient and donor age were 52 years (range, 19 to 75) and 38 years (range, 15 to 73), peripheral blood stem cell was the stem cell source in 66%, and myeloablative conditioning was used in 41%. Median follow-up for surviving patients was 33 months (range, 7 to 130). Donor variables analyzed included age, sex, relationship, cytomegalovirus (CMV) status, ABO compatibility, HLA disparity, and several natural killer (NK) alloreactivity models. Multivariate Cox analysis was used to adjust for known patient, disease, and transplant covariates. Donor characteristics independently associated with improved survival included presence of HLA-DR mismatch, HLA-DP nonpermissive mismatch, killer cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch, and KIR B/x haplotype with KIR2DS2. Donor characteristics associated with inferior survival included parental donor relationship and the use of a CMV-seronegative donor for a CMV-seropositive patient. Increased HLA disparity (≥4/10 HLA allelic mismatches [graft-versus-host direction]) resulted in relapse protection at the expense of increased nonrelapse mortality with no associated survival effect. We further propose a donor risk factor scoring system to permit a more evidence-based selection algorithm for potential haplo donors. This large, single-institution analysis demonstrates the importance of HLA-DR/HLA-DP disparity, NK alloreactivity, and other clinical variables in the haplo donor selection process and suggests that KIR and HLA-DP genotyping should be performed routinely for haplo donor selection.

show abstract

Section: Discussionmentioning

confidence: 90%

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

Solomon

Aubrey²,

Zhang

et al. 2018

Biology of Blood and Marrow Transplantation

101

View full text Add to dashboard Cite

show abstract

“…Although donor group B genotypes (Bx) are preferable, our previous studies showed a risk of decreased survival in transplants from Bx2 donors . The KIR Bx2 (A/B1) genotype carried B‐specific KIR genes 3DS1 , 2DL5A , 2DS5 , and 2DS1 on the telomeric motif.…”

Section: Resultsmentioning

confidence: 99%

“…Although donor group B genotypes (Bx) are preferable, our previous studies showed a risk of decreased survival in transplants from Bx2 donors. 9,31 The KIR Bx2 (A/B1) genotype carried B-specific KIR genes 3DS1, 2DL5A, 2DS5, and 2DS1 on the telomeric motif. It was reported that the allelic products of 2DS5 differed in their levels of expression, 32,33 Also, the Tel-KIR2DS5 alleles had a reduced avidity for the C2 epitope of HLA-C, 32 and Cen-KIR2DS5 was reported to be protective.…”

Section: Discussion and Future Researchmentioning

confidence: 99%

Population‐specific criterion to distinguish killer cell immunoglobulin‐like receptor genotypes and haplotypes in a large Eastern Han population

Bao

Zhang

et al. 2019

HLA

Self Cite

View full text Add to dashboard Cite

With the goal of improving the population‐specific criteria to distinguish KIR genotypes and haplotypes in the region, we examined the KIR gene and haplotype data of Eastern Han based on a large population and analyzed the component genes of centromeric (Cen) and telomeric (Tel) KIR haplotype segments, which may differ in the protection they provide in hematopoietic stem cell transplantation. Samples from 598 families and 2845 unrelated individuals of Eastern Han origin were collected between 2010 and 2017. Genotyping of 17 KIR genes was performed by PCR‐SSP and SSO methods. The results showed we obtained the KIR gene distribution of the Eastern Han population. The KIR gene frequencies (GF) in the present study are similar to those observed in other studies on Han but different from other populations. We observed a total of 56 different genotypes, including 1 AA and 55 group B genotypes. The high‐frequency KIR genotype profiles found in the present population were consistent with other studies on Han populations but different from those conducted on other populations. In the family panel, a total of 28 KIR haplotypes were identified in the segregation study. The majority of Eastern Han carried group A KIR gene motifs. Comparison of the frequencies of Cen and Tel KIR gene motifs shows that they differ from other populations. The study on the distribution of KIR genes in the population may aid in the development of a complementary population‐specific criterion to distinguish between KIR haplotypes and offer a research direction for further gene functional studies.

show abstract

“…3,12 One could potentially exploit this property by selecting donors either for NK-CAR production based on KIR-ligand mismatch with the recipient or based on haplotype B KIR gene content, as both have been shown to be beneficial in the setting of allogeneic stem cell transplantation. 27,[75][76][77][78] Initial reluctance to utilize NK cells for CAR-modified therapy was largely based on the uncertainty regarding their ability to migrate to and penetrate tumor tissues, and their presumed overall inferiority to CAR-T cells. 79 Part of this reluctance is related to the limited in vivo persistence of NK cells, which, while desirable from a safety standpoint, may be limiting from an efficacy standpoint.…”

Section: Advantages and Challenges Of Car-nk Cell Therapymentioning

confidence: 99%

Engineering Natural Killer Cells for Cancer Immunotherapy

et al. 2017

View full text Add to dashboard Cite

The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification. We will discuss strategies to introduce CARs into both primary NK cells and NK cell lines in an effort to provide antigen specificity, the challenges of manufacturing engineered NK cells, and evidence supporting the effectiveness of this approach from preclinical and early-phase clinical studies using CAR-engineered NK cells. CAR-NK cells hold great promise as a novel cellular immunotherapy against refractory malignancies. Notably, NK cells can provide an "off-the-shelf" product, eliminating the need for a personalized and patient-specific product that plagues current CAR-T cell therapies. The ability to more potently direct NK cell-mediated cytotoxicity against refractory tumors through the expression of CAR is likely to contribute to the recent paradigm shift in cancer treatment.

show abstract

Donor Killer Immunoglobulin-Like Receptor Profile Bx1 Imparts a Negative Effect and Centromeric B-Specific Gene Motifs Render a Positive Effect on Standard-Risk Acute Myeloid Leukemia/Myelodysplastic Syndrome Patient Survival after Unrelated Donor Hematopoietic Stem Cell Transplantation

Cited by 15 publications

References 29 publications

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

Population‐specific criterion to distinguish killer cell immunoglobulin‐like receptor genotypes and haplotypes in a large Eastern Han population

Engineering Natural Killer Cells for Cancer Immunotherapy

Contact Info

Product

Resources

About