更新于：2024-11-01

KIR2DL2 x CD19

更新于：2024-11-01

基本信息

关联

项与 KIR2DL2 x CD19 相关的药物

KIR2DL2 depleted CD19-CAR-T (H. Lee Moffitt Cancer Center & Research Institute)

靶点

CD19 x KIR2DL2

作用机制

CD19抑制剂 [+1]

在研机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

原研机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 KIR2DL2 x CD19 相关的临床结果

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100 项与 KIR2DL2 x CD19 相关的转化医学

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0 项与 KIR2DL2 x CD19 相关的专利（医药）

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项与 KIR2DL2 x CD19 相关的文献（医药）

2012-11-15·Clinical Cancer Research1区 · 医学

Antibody-Dependent Cell-Mediated Cytotoxicity Overcomes NK Cell Resistance in MLL-Rearranged Leukemia Expressing Inhibitory KIR Ligands but Not Activating Ligands

1区 · 医学

Article

作者: Chan, Wing Keung ; Schell, Sarah ; Li, Ying ; Zalevsky, Jonathan ; Leung, Wing ; Kung Sutherland, May

AbstractPurpose: Leukemias with MLL gene rearrangement are associated with a poor prognosis. Natural killer (NK) cell therapy is a potential treatment, but leukemia cells may be resistant. Here, we sought to determine the susceptibility of MLL-rearranged leukemia cells to NK cell lysis and to develop a novel immunotherapeutic approach to optimize NK cell therapy, including the use of an antibody against leukemia-associated antigen and the elimination of killer-cell immunoglobulin-like receptor (KIR)–mediated inhibition.Experimental Design: Three MLL-rearranged leukemia cell lines (RS4;11, SEM, and MV4-11) and primary leukemia blasts were assessed for surface phenotype and susceptibility to NK cell lysis with or without antibodies against CD19 (XmAb5574), CD33 (lintuzumab), or KIR ligands.Results: All three cell lines were resistant to NK cell lysis, had some inhibitory KIR ligands and protease inhibitor-9, and expressed low levels of NKG2D activating ligands and adhesion molecules. After treatment with XmAb5574 or lintuzumab, MLL-rearranged leukemia cells were efficiently killed by NK cells. The addition of pan–major histocompatibility complex class I antibody, which blocked inhibitory KIR-HLA interaction, further augmented degranulation in all three KIR2DL1, KIR2DL2/3, and KIR3DL1 subsets of NK cells based on the rule of missing-self recognition. A mouse model showed a decreased rate of leukemia progression in vivo as monitored by bioluminescence imaging and longer survival after antibody treatment.Conclusion: Our data support the use of a triple immunotherapy approach, including an antibody directed against tumor-associated antigen, KIR-mismatched NK cell transplantation, and inhibitory KIR blockade, for the treatment of NK cell–resistant MLL-rearranged leukemias. Clin Cancer Res; 18(22); 6296–305. ©2012 AACR.

2010-06-01·Cancer Epidemiology3区 · 医学

Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia

3区 · 医学

Article

作者: David Finkelstein ; Ching Hon Pui ; Wing Leung ; Fred Behm ; Michael B. Kastan ; Rekha Iyengar ; Geoffrey Neale

BACKGROUNDSurvivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage.METHODSComparative studies on 14 survivors in first complete remission and 16 siblings were conducted.RESULTSIn comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (alphabetaT cells and CD45RO+/RA- memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (gammadeltaT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO-/RA+ naïve T cell and less SjTREC levels in the blood, whereas the Vbeta spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole-genome scanning by SNP microarray analysis.CONCLUSIONALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy.

2010-05-01·Experimental Hematology4区 · 医学

Natural-killer cell amplification for adoptive leukemia relapse immunotherapy: Comparison of three cytokines, IL-2, IL-15, or IL-7 and impact on NKG2D, KIR2DL1, and KIR2DL2 expression

4区 · 医学

Article

作者: Véronique Decot ; Lamia Aissi-Rothé ; Daniele Bensoussan ; Jean Francois Stoltz ; Véronique Latger-Cannard ; Pascale Perrier ; Laure Voillard

OBJECTIVENatural killer (NK) cells are a lymphocyte subset that, in a hematopoietic stem cell transplantation setting, mediates a graft-vs-leukemia effect without any graft-vs-host disease. We aimed to evaluate an isolation method that can be used with Good Manufacturing Practices-grade reagents and to compare three cytokines for expansion in order to design future clinical protocols based on donor NK-cell infusions to cure relapse after allograft.MATERIALS AND METHODSNK cells were enriched using a CD3/CD19 depletion method and expanded for 13 days in the presence of 2, 10, and 50 ng/mL interleukin (IL)-2, IL-15, or IL-7. NK-cell cytotoxicity was evaluated after isolation and culture. Expression of NKG2D, KIR2DL2, and KIR2DL1 was monitored during expansion.RESULTSHighly T- and B-cell-depleted NK cells were obtained and enriched 2.6-fold. The optimal cytokine concentration for expansion was 10 ng/mL for IL-2 or 50 ng/mL for IL-15. NK-cell cytotoxicity was significantly improved after an overnight incubation with 10 or 50 ng/mL IL-2 or with 2, 10, or 50 ng/mL IL-15, and after 13 days with 50 ng/mL IL-15. The use of a combination of IL-2 and IL-15 showed no additional benefit and negative results were obtained with IL-7. The three NK cell receptors were significantly upregulated after culture, mainly with IL-2 or IL-15.CONCLUSIONIn our study, 10 ng/mL IL-2 or 50 ng/mL IL-15 were the optimal concentrations for expansion and were equivalent in significantly enhancing cytotoxicity and modifying NK-cell receptor expression patterns.