更新于：2024-11-01

IL-12R x IL18R1

更新于：2024-11-01

基本信息

关联

项与 IL-12R x IL18R1 相关的药物

SON-1411

靶点

IL-12R x IL18R1

作用机制

IL-12R调节剂 [+1]

在研机构

Sonnet BioTherapeutics, Inc.

原研机构

Sonnet BioTherapeutics, Inc.

在研适应症

实体瘤

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

HCW-9201

靶点

IL-12R x IL15R x IL18R1

作用机制

IL-12R刺激剂 [+3]

在研机构-

原研机构

HCW Biologics Inc.

在研适应症-

非在研适应症

急性髓性白血病 [+1]

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

100 项与 IL-12R x IL18R1 相关的临床结果

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100 项与 IL-12R x IL18R1 相关的转化医学

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0 项与 IL-12R x IL18R1 相关的专利（医药）

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项与 IL-12R x IL18R1 相关的文献（医药）

2024-07-01·Lung Cancer

Differences in microenvironment of lung cancer and pleural effusions by single-cell RNA sequencing

Article

作者: Dorry, Michael ; Yi, John ; Ji, Zhicheng ; Shofer, Scott L ; Wahidi, Momen M ; Clarke, Jeffrey M ; Mahmood, Kamran ; Shaz, Beth H ; Steadman, Katelyn ; Giovacchini, Coral X ; Weinhold, Kent J ; Antonia, Scott J ; Wang, Huimin

BACKGROUNDDirect comparison of tumor microenvironment of matched lung cancer biopsies and pleural effusions (PE) from the same patients is critical in understanding tumor biology but has not been performed. This is the first study to compare the lung cancer and PE microenvironment by single-cell RNA sequencing (scRNA-seq).METHODSMatched lung cancer biopsies and PE were obtained prospectively from ten patients. We isolated CD45⁺ cells and performed scRNA-seq to compare the biopsies and PE.RESULTSPE had a higher proportion of CD4⁺ T cells but lower proportion of CD8⁺ T cells (False detection rate, FDR = 0.0003) compared to biopsies. There was a higher proportion of naïve CD4⁺ T cells (FDR = 0.04) and naïve CD8⁺ T cells (FDR = 0.0008) in PE vs. biopsies. On the other hand, there was a higher proportion of Tregs (FDR = 0.04), effector CD8⁺ (FDR = 0.006), and exhausted CD8⁺ T cells (FDR = 0.01) in biopsies. The expression of inflammatory genes in T cells was increased in biopsies vs. PE, including TNF, IFN-ɣ, IL-1R1, IL-1R2, IL-2, IL-12RB2, IL-18R1, and IL-18RAP (FDR = 0.009, 0.013, 0.029, 0.043, 0.009, 0.013, 0.004, and 0.003, respectively). The gene expression of exhaustion markers in T cells was also increased in tumor biopsies including PDCD1, CTLA4, LAG 3, HAVCR2, TIGIT, and CD160 (FDR = 0.008, 0.003, 0.002, 0.011, 0.006, and 0.049, respectively).CONCLUSIONSThere is a higher proportion of naïve T cells and lower proportion of exhausted T cells and Tregs in PE compared to lung cancer biopsies, which can be leveraged for prognostic and therapeutic applications.

2020-08-01·Clinical Immunology

Racial disparity in Covid-19 mortality rates - A plausible explanation

Letter

作者: Irit Adini ; Yuval Tal ; Avner Adini ; Alal Eran

Using RNAseq gene anal. data from the Genotype-Tissue Expression (GTEx) project, we compared the expression of cytokines and other central immune modulators between healthy black and white Americans.We found that infammasome-derived interleukin 1 beta (IL1β) and interleukin 18 receptor 1 (IL18R1) were up-regulated in black individuals (fold change (FC) = 2.25 and 2.21, resp.; P < .01), other cytokines such as interleukin-12 receptor beta 1 (IL12Rβ1) expression was also elevated (FC = 1.62).Furthermore, we detected elevated expression of innate immunity receptors responsible for ssRNA recognition (TLR7) and non-methylated CpG sequence binding of bacterial or viral DNA (TLR9). (FC = 1.81; FC = 1.22; resp., P < .01).These variation in gene expression prompted us to investigate bio-chem. pathway discrepancies that would support our hypothesis and would help illuminate personalized treatment options.Our findings suggest that black individuals may have the tendency to develop a harsher pro-inflammatory cytokine response.Accordingly, we posit that when confronted with SARS-cov-2, black Americans would be more prone to develop a rapid and more aggressive cytokine storm.

2019-12-01·BMC Genomics2区 · 生物学

Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies

2区 · 生物学

ArticleOA

作者: Maranhão, Andréa Queiroz ; Hoffmann, Steve ; Simi, Kelly Cristina Rodrigues ; Bezerra, Maryani Andressa Gomes ; Doose, Gero ; Stadler, Peter F ; Brigido, Marcelo Macedo ; Sousa, Isabel Garcia ; Raiol, Tainá ; do Almo, Manuela Maragno

BACKGROUNDAnti-CD3 immunotherapy was initially approved for clinical use for renal transplantation rejection prevention. Subsequently, new generations of anti-CD3 antibodies have entered clinical trials for a broader spectrum of therapeutic applications, including cancer and autoimmune diseases. Despite their extensive use, little is known about the exact mechanism of these molecules, except that they are able to activate T cells, inducing an overall immunoregulatory and tolerogenic behavior. To better understand the effects of anti-CD3 antibodies on human T cells, PBMCs were stimulated, and then, we performed RNA-seq assays of enriched T cells to assess changes in their gene expression profiles. In this study, three different anti-CD3 antibodies were used for the stimulation: two recombinant antibody fragments, namely, a humanized and a chimeric FvFc molecule, and the prototype mouse mAb OKT3.RESULTSGene Ontology categories and individual immunoregulatory markers were compared, suggesting a similarity in modulated gene sets, mainly those for immunoregulatory and inflammatory terms. Upregulation of interleukin receptors, such as IL2RA, IL1R, IL12RB2, IL18R1, IL21R and IL23R, and of inhibitory molecules, such as FOXP3, CTLA4, TNFRSF18, LAG3 and PDCD1, were also observed, suggesting an inhibitory and exhausted phenotype.CONCLUSIONSWe used a deep transcriptome sequencing method for comparing three anti-CD3 antibodies in terms of Gene Ontology enrichment and immunological marker expression. The present data showed that both recombinant antibodies induced a compatible expression profile, suggesting that they might be candidates for a closer evaluation with respect to their therapeutic value. Moreover, the proposed methodology is amenable to be more generally applied for molecular comparison of cell receptor dependent antibody therapy.