An Open-label Phase I Dose-escalation Study to Evaluate the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetics, and Pharmacodynamics of the Anti-C4.4a Antibody Drug Conjugate BAY1129980 in Subjects With Advanced Solid Tumors Known to Express C4.4a

The purpose of this study is to evaluate:
The side effects of BAY1129980 when given every 21 days different dose levels.
Determine the dose level of BAY1129980 that should be tested in future clinical research studies.
Measure how much BAY1129980 is in the blood at specific times after administration.
If treatment with BAY1129980 shows any effect on reducing the tumor growth.
If there are specific biomarkers that might be able to explain why some patients respond to treatment and others do not.
If treatment with BAY1129980 causes an immune response from the body against the drug (immunogenicity).

Start Date22 May 2014

Sponsor / Collaborator

Bayer AG

100 Clinical Results associated with LYPD3

100 Translational Medicine associated with LYPD3

0 Patents (Medical) associated with LYPD3

Literatures (Medical) associated with LYPD3

01 Nov 2024·Gene

Transcriptome analysis of human dental pulp cells cultured on a novel cell-adhesive fragment by RNA sequencing

Article

Author: Huang, Xiaofeng ; Tang, Jia

AIMThe aim of the present work was to find an efficient method for safe and reliable expansion of human dental pulp cells (hDPCs) in vitro. Here, we examined the effect of a novel recombinant E8 fragment of Laminin-511 (iMatrix-511) in hDPCs regarding viability and cell spreading. Further, we investigated the underlying mechanisms governing its effects in hDPCs using RNA sequencing (RNA-seq).METHODOLOGYhDPCs were obtained from caries-free maxilla third molars (n = 3). CCK-8 assay was conducted to measure the viability of cells cultured on iMatrix-511 and two other ECM proteins. Cell morphology was observed by phase contrast microscope. RNA-seq of hDPCs cultured on iMatrix-511 or noncoated control was performed on Illumina Novaseq^TM 6000 platform.RESULTSiMatrix-511 (0.5 μg/cm²) enhanced the viability of hDPCs to an extent better than COL-1 and gelatin. Short term culture of hDPCs on iMatrix-511 resulted in 233 differentially expressed genes (DEGs). The top 12 most upregulated genes were XIAP, AL354740, MRFAP1, AC012321, KCND3, TMEM120B, AC009812, GET1-SH3BGR, CNTN3, AC090409, GEN1 and PIK3IP1, whereas the top 12 most downregulated genes were SFN, KRT17, RAB4B-EGLN2, CSTA, KCTD11, ATP6V1G2-DDX39B, AC010323, SBSN, LYPD3, FOSB, AC022400 and CHI3L1. qPCR validation confirmed the significant upregulation of GEN1, KCND3, PIK3IP1 and MRFAP1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, with genes enriched in various extracellular matrix interaction, estrogen and fat metabolism-related functions and pathways.CONCLUSIONSiMatrix-511 facilitated spreading and proliferation of hDPCs. It enhances expression of anti-apoptotic genes, while inhibits expression of epidermis development-related genes.

01 Mar 2024·Translational Cancer Research

Comprehensive analysis of exosome gene LYPD3 and prognosis/immune cell infiltration in lung cancer

Article

Author: Li, Gui-Zhen ; Jia, Chenghui ; Xin, Tao ; Zheng, Chunlong ; Jing, Pengyu ; Lu, Qiang ; Xu, Xinyao ; Zhang, Jipeng

BackgroundLung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC.MethodsWe used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC. We applied Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (KM) plotter to evaluate the prognostic prediction performance of LYPD3. Biological processes (BPs), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) analyses were performed to illustrate the possible role of LYPD3 in LC. The correlations between LYPD3 and immune cell infiltration were explored using Tumor and Immune System Interaction Database (TISIDB), GEPIA2, and TIMER. R software was used for statistical analysis and mapping.ResultsA total of 904 exosome molecules were screened in LC. Further analysis showed that the up-regulation of LYPD3 in these 904 exosome molecules was associated with poor prognosis in LC. Pan-cancer analyses revealed that the expression of LYPD3 varied in many cancers, particularly in LC. Clinical correlation analysis indicated that LYPD3 was associated with stage and T classification in LC. We observed that LYPD3 co-expression genes were associated with cell cycle, DNA replication, proteasome, and regulation of the actin cytoskeleton by GSEA. Moreover, LYPD3 was associated with immune modulators. Immunophenoscores (IPS) and IPS-CTLA4 were significantly different between the high LYPD3 group and low LYPD3 group. Additionally, the median half maximal inhibitory concentration (IC₅₀) of bexarotene, cyclopamine, etoposide, and paclitaxel in LYPD3 high group was significantly lower than that in LYPD3 low group.ConclusionsLYPD3 is involved in many BPs of LC, such as regulating immune cell infiltration and affecting prognosis. Therefore, LYPD3 may have potential value as a biomarker for prognosis and immunotherapy in LC.

01 Nov 2023·Heliyon

Constructing an APOBEC-related gene signature with predictive value in the overall survival and therapeutic sensitivity in lung adenocarcinoma

Article

Author: Yang, Yanni ; Wu, Ruixin ; Zhong, Jian ; Shi, Jianrong ; Wang, Huiru ; Luo, Yu ; Zhang, Xianlin

BackgroundAPOBEC family play an important role in cancer mutagenesis and tumor development. The role of APOBEC family in lung adenocarcinoma (LUAD) has not been studied comprehensively.Materials and methodsThe expression data of pan-cancer as well as LUAD was obtained from public databases. The expression level of APOBEC family genes was analyzed in different normal and cancer tissues. APOBEC mutagenesis enrichment score (AMES) was utilized to evaluate the APOBEC-induced mutations and the relation of APOBEC with genomic instability. Gene set enrichment analysis was used to identify differentially enriched pathways. Univariate Cox regression and Lasso regression were applied to screen key prognostic genes. The immune cell infiltration was estimated by CIBERSORT. RT-qPCR assay, CCK-8 and Transwell assay were conducted to explore gene expression and lung cancer cell invasion.ResultsCancer tissues had significantly altered expression of APOBEC family genes and the expression patterns of APOBEC family were different in different cancer types. APOBEC3B was the most aberrantly expressed in most cancer types. In LUAD, we observed a significantly positive correlation of AMES with intratumor heterogeneity (ITH), tumor neoantigen burden (TNB), and tumor mutation burden (TMB). High AMES group had high mutation counts of DNA damage repair pathways, and high enrichment of cell cycle and DNA repair pathways. We identified four prognostic genes (LYPD3, ANLN, MUC5B, and FOSL1) based on AMES, and constructed an AMES-related gene signature. The expressions of four genes were enhanced and accelerated the invasion ability and viability of lung cancer cells. Furthermore, we found that high group increased oxidative stress level.ConclusionsAPOBEC family was associated with genomic instability, DNA damage-related pathways, and cell cycle in LUAD. The AMES-related gene signature had a great potential to indicate the prognosis and guide immunotherapy/chemotherapy for patients suffering from LUAD.

News (Medical) associated with LYPD3

08 Nov 2022

·www.globenewswire.com

Glycotope Presents GlycoTarget Platform and New Data on Platform-Derived anti-LYPD3 Antibody at 2022 Society for Immunotherapy of Cancer (SITC) Meeting

Glycotope Presents GlycoTarget Platform and New Data on Platform-Derived anti-LYPD3 Antibody at 2022 Society for Immunotherapy of Cancer (SITC) Meeting Berlin, Germany, 08 November, 2022 – Glycotope GmbH, a biotechnology company with a proprietary platform technology for developing antibodies against proteins carrying tumor-specific carbohydrate structures, today announces that it will present new data at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting, being held in Boston, United States, between 8-12 November 2022. Patrik Kehler, Chief Scientific Officer of Glycotope GmbH commented: “We are looking forward to providing an update on the progress of our lead antibody program, GT-002, at SITC. The glycosylation-dependent binding of LYPD3 by GT-002 leads to markedly improved tumor-selectivity compared to protein binding antibodies resulting in reduced binding to healthy tissues. In addition, we will deliver a presentation on our GlycoTarget platform, showcasing how, by utilizing the same principle, our technology can be applied to significantly improve selectivity across other targets beside LYPD3.” Poster details are as follows: Abstract Number: 1347 Download here from Thursday, 10 November 8am EST Title: Targeting of a cancer-associated LYPD3 glycoform for tumor therapy Poster hall: 10 November 2022, 9:00am - 9:00pm EST Abstract Number: 1346 Download here from Friday, 11 November 8am EST Title: Antibodies against GlycoTargets as novel platform approach to address unmet needs in cancer therapy Poster hall: 11 November 2022, 9:00am - 9:00pm EST Abstracts will be available on SITC’s website located at www.sitcancer.org at 8am EST on Nov. 7, 2022 Contact Information: Glycotope GmbH Dr. Patrik Kehler (CSO) Phone: +49 30 9489 2600 Email: contact@glycotope.com Media Contact: Chris Gardner, Chris Welsh Consillium Strategic Communications Phone: +44 20 3709 5700 Email: glycotope@consillium-comms.com About GT-002 Antibodies targeting LYPD3 (C4.4A) with increased tumor-specificity. LYPD3 is expressed in various cancer indications with high medical need, including squamous cell carcinoma of the head and neck (HNSCC). Upon binding to LYPD3, the antibody is effectively internalized. The improved tumor-specificity of GT-002 results in reduced binding to healthy-tissue expressed LYPD3 making it suitable for the development of highly potent therapies like ADCs, CARs or radio pharmaceutics. About Glycotope Glycotope is a biotechnology company utilizing a proprietary technology platform to develop uniquely tumor-specific monoclonal antibodies. Our antibodies target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glyco-epitopes (GlycoTargets). Glycotope has to date discovered in excess of 200 GlycoTargets with antibodies against several of these targets currently under development. Based on their superior tumor-specificity, our antibodies are suitable for development in an array of different modes of action including naked antibodies, bispecifics, antibody-drug-conjugates, cellular therapies or fusion-proteins. Visit www.glycotope.com

CollaborateAntibodySmall molecular drugImmunotherapyADC

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

LYPD3

Basic Info

Related

Analysis