更新于：2024-11-01

B2M x HLA-B

更新于：2024-11-01

基本信息

关联

项与 B2M x HLA-B 相关的药物

Velimogene aliplasmid

靶点

B2M x HLA-B

作用机制

B2M抑制剂 [+1]

在研机构-

原研机构

Vical, Inc.

在研适应症-

非在研适应症

复发性黑色素瘤 [+3]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 B2M x HLA-B 相关的临床试验

NCT00395070 / Completed临床3期

A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Treatment With 2 mg Intralesional Allovectin-7® Compared to Dacarbazine (DTIC) or Temozolomide (TMZ) in Subjects With Recurrent Metastatic Melanoma

To compare the safety and efficacy of Allovectin-7® versus Dacarbazine (DTIC)or Temozolomide (TMZ) in subjects with recurrent stage 3 or stage 4 melanoma.

开始日期2006-10-01

申办/合作机构

Vical, Inc.

NCT00044356 / Completed临床2期

A Phase II Study of High-Dose Allovectin-7® in Patients With Advanced Metastatic Melanoma

The purpose of this clinical trial is to determine if Allovectin-7®, an experimental gene-based immunotherapy, can shrink melanoma tumors. The trial will also examine if this treatment can improve the time to disease progression.

开始日期2001-02-01

申办/合作机构

Vical, Inc.

NCT00003646 / Completed临床2期

Phase II Study of Allovectin-7 as an Immunotherapeutic Agent in Patients With Stages III and IV Melanoma

RATIONALE: Injecting allovectin-7 into a person's melanoma cells may make the body build an immune response that will kill tumor cells.
PURPOSE: Phase II trial to study the effectiveness of gene therapy in treating patients who have stage III or stage IV melanoma that has not responded to previous treatment.

开始日期1998-08-01

申办/合作机构

Vical, Inc.

100 项与 B2M x HLA-B 相关的临床结果

登录后查看更多信息

100 项与 B2M x HLA-B 相关的转化医学

登录后查看更多信息

0 项与 B2M x HLA-B 相关的专利（医药）

登录后查看更多信息

项与 B2M x HLA-B 相关的文献（医药）

2024-01-01·Cancer Immunology, Immunotherapy

Allogeneic CAR-T cells with of HLA-A/B and TRAC disruption exhibit promising antitumor capacity against B cell malignancies

Article

作者: Li, Ling ; Xing, Haizhou ; Li, Wei ; Tan, Binghe ; Cao, Weijie ; Huang, Jianmin ; Ping, Yu ; Chen, Xinfeng ; Zhang, Yi ; Liu, Mingyao ; Lin, Boxu ; Du, Bing ; Li, Xin ; Zhang, Mingzhi ; Zhang, Xudong ; Jiang, Zhongxing ; Zhang, Na ; Zhao, Xuan ; Zhang, Zhen ; Shi, Xiujuan

AbstractBackgroundAlthough chimeric antigen receptor T (CAR-T) cells have been proven to be an effective way of treating B cell malignancies, a lot of patients could not benefit from it because of failure in CAR-T cell manufacturing, disease progression, and unaffordable price. The study aimed to explore universal CAR-T cell products to extend the clinical accessibility.MethodsThe antitumor activity of CRISPR/Cas9-edited allogeneic anti-CD19 CAR-T (CAR-T19) cells was assessed in vitro, in animal models, and in patients with relapsed/refractory (R/R) acute B cell lymphoblastic leukemia (B-ALL) or diffuse large B cell lymphoma.ResultsB2M−/TRAC− universal CAR-T19 (U-CAR-T19) cells exhibited powerful anti-leukemia abilities both in vitro and in animal models, as did primary CD19+ leukemia cells from leukemia patients. However, expansion, antitumor efficacy, or graft-versus-host-disease (GvHD) was not observed in six patients with R/R B cell malignancies after U-CAR-T19 cell infusion. Accordingly, significant activation of natural killer (NK) cells by U-CAR-T19 cells was proven both clinically and in vitro. HLA-A−/B−/TRAC− novel CAR-T19 (nU-CAR-T19) cells were constructed with similar tumoricidal capacity but resistance to NK cells in vitro. Surprisingly, robust expansion of nU-CAR-T19 cells, along with rapid eradication of CD19+ abnormal B cells, was observed in the peripheral blood and bone marrow of another three patients with R/R B-ALL. The patients achieved complete remission with no detectable minimal residual disease 14 days after the infusion of nU-CAR-T19 cells. Two of the three patients had grade 2 cytokine release syndrome, which were managed using an IL-6 receptor blocker. Most importantly, GvHD was not observed in any patient, suggesting the safety of TRAC-disrupted CAR-T cells generated using the CRISPR/Cas9 method for clinical application.ConclusionsThe nU-CAR-T19 cells showed a strong response in R/R B-ALL. nU-CAR-T19 cells have the potential to be a promising new approach for treating R/R B cell malignancies.

2022-03-01·Journal for ImmunoTherapy of Cancer2区 · 医学

T cell receptor engineering of primary NK cells to therapeutically target tumors and tumor immune evasion

2区 · 医学

ArticleOA

作者: van Loenen, Marleen M ; Morton, Laura T ; Meeuwsen, Miranda H ; Remst, Dennis F G ; Heemskerk, Mirjam H M ; Wachsmann, Tassilo L A ; Wouters, Anne K ; Falkenburg, J H Frederik

BackgroundT cell receptor (TCR)-engineered cells can be powerful tools in the treatment of malignancies. However, tumor resistance by Human Leukocyte antigen (HLA) class I downregulation can negatively impact the success of any TCR-mediated cell therapy. Allogeneic natural killer (NK) cells have demonstrated efficacy and safety against malignancies without inducing graft-versus-host-disease, highlighting the feasibility for an ‘off the shelf’ cellular therapeutic. Furthermore, primary NK cells can target tumors using a broad array of intrinsic activation mechanisms. In this study, we combined the antitumor effector functions of NK cells with TCR engineering (NK-TCR), creating a novel therapeutic strategy to avoid TCR-associated immune resistance.MethodsBOB1, is a transcription factor highly expressed in all healthy and malignant B cell lineages, including multiple myeloma (MM). Expression of an HLA-B*07:02 restricted BOB1-specifc TCR in peripheral blood–derived NK cells was achieved following a two-step retroviral transduction protocol. NK-TCR was then compared with TCR-negative NK cells and CD8-T cells expressing the same TCR for effector function against HLA-B*07:02+ B-cell derived lymphoblastoid cell lines (B-LCL), B-cell acute lymphoblastic leukemia and MM cell lines in vitro and in vivo.ResultsFirstly, TCR could be reproducibly expressed in NK cells isolated from the peripheral blood of multiple healthy donors generating pure NK-TCR cell products. Secondly, NK-TCR demonstrated antigen-specific effector functions against malignancies which were previously resistant to NK-mediated lysis and enhanced NK efficacy in vivo using a preclinical xenograft model of MM. Moreover, antigen-specific cytotoxicity and cytokine production of NK-TCR was comparable to CD8 T cells expressing the same TCR. Finally, in a model of HLA-class I loss, tumor cells with B2M KO were lysed by NK-TCR in an NK-mediated manner but were resistant to T-cell based killing.ConclusionNK-TCR cell therapy enhances NK cell efficacy against tumors through additional TCR-mediated lysis. Furthermore, the dual efficacy of NK-TCR permits the specific targeting of tumors and the associated TCR-associated immune resistance, making NK-TCR a unique cellular therapeutic.

2022-01-01·Bioinformatics and Biology Insights

Bioinformatics Approach to Identify Significant Biomarkers, Drug Targets Shared Between Parkinson’s Disease and Bipolar Disorder: A Pilot Study

Article

作者: Rahaman, Abidur ; Adhikary, Apurba ; Hossain, Md. Bipul ; Islam, Md. Kobirul ; Islam, Md. Zahidul

Parkinson’s disease (PD) is a neurodegenerative disorder responsible for shaking, rigidity, and trouble in walking and patients’ coordination ability and physical stability deteriorate day by day. Bipolar disorder (BD) is a psychiatric disorder which is the reason behind extreme shiftiness in mood, and frequent mood inversion may reach too high called mania. People with BD have a greater chance of developing PD during the follow-up period. A lot of work has been done to understand the key factors for developing these 2 diseases. But the molecular functionalities that trigger the development of PD in people with BD are not clear yet. In our study, we are intended to identify the molecular biomarkers and pathways shared between BD and PD. We have investigated the RNA-Seq gene expression data sets of PD and BD. A total of 45 common unique genes (32 up-regulated and 13 down-regulated) abnormally expressed in both PD and BD were identified by applying statistical methods on the GEO data sets. Gene ontology (GO) and BioCarta, KEGG, and Reactome pathways analysis of these 45 common dysregulated genes identified numerous altered molecular pathways such as mineral absorption, Epstein-Barr virus infection, HTLV-I infection, antigen processing, and presentation. Analysis of protein-protein interactions revealed 9 significant hub-proteins, namely RPL21, RPL34, CKS2, B2M, TNFRSF10A, DTX2, HLA-B, ATP2A3, and TAPBP. Significant transcription factors (IRF8, SPI1, RUNX1, and FOXA1) and posttranscriptional regulator microRNAs (hsa-miR-491-3p and hsa-miR-1246) are also found by analyzing gene-transcription factors and gene-miRNAs interactions, respectively. Protein-drug interaction analysis revealed hub-protein B2M’s interaction with molecular drug candidates like N-formylmethionine, 3-indolebutyric acid, and doxycycline. Finally, a link between pathological processes of PD and BD is identified at transcriptional level. This study may help us to predict the development of PD among the people suffering from BD and gives some clue to understand significant pathological mechanisms.