A5050625719- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Radiopharmaceutical Chemistry and Applications
- Advanced Biosensing Techniques and Applications
- Nanoparticle-Based Drug Delivery
- Cancer Research and Treatments
- Barrier Structure and Function Studies
- Brain Metastases and Treatment
- Innovative Microfluidic and Catalytic Techniques Innovation
- Thyroid Disorders and Treatments
- Caveolin-1 and cellular processes
- Glycosylation and Glycoproteins Research
- Cancer Treatment and Pharmacology
- Microtubule and mitosis dynamics
- Natural product bioactivities and synthesis
- Cell Adhesion Molecules Research
- Plant biochemistry and biosynthesis
- Thyroid Cancer Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Breast Lesions and Carcinomas
- Fibroblast Growth Factor Research
- Phytochemicals and Antioxidant Activities
- Cancer Cells and Metastasis
- Traditional and Medicinal Uses of Annonaceae
- Lung Cancer Treatments and Mutations
University of Southern California
2016-2023
USC Norris Comprehensive Cancer Center
2023
University of Wales
1988
Allgemeines Krankenhaus Celle
1988
University of Nottingham
1988
Universität Hamburg
1988
University of Liverpool
1966-1967
Abstract Purpose: Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression normal adult tissue. This profile makes CLDN6 an ideal target for development of a potential therapeutic antibody–drug conjugate (ADC). study describes the generation preclinical characterization CLDN6–23-ADC, ADC consisting humanized anti-CLDN6 monoclonal antibody coupled to monomethyl auristatin E (MMAE) via...
The methods (IHC/FISH) typically used to assess ER, PR, HER2, and Ki67 in FFPE specimens from breast cancer patients are difficult set up, perform, standardize for use low middle-income countries. Use of an automated diagnostic platform (GeneXpert®) assay (Xpert® Breast Cancer STRAT4) that employs RT-qPCR quantitate ESR1, PGR, ERBB2, MKi67 mRNAs formalin-fixed, paraffin-embedded (FFPE) tissues facilitates analyses less than 3 h. This study compares biomarker using RT-qPCR-based with standard...
Significance Polo-like kinase 4 (PLK4), a known cell cycle regulatory protein, localizes to the centrosome during S-phase and facilitates duplication. We show that phospho-serine305-PLK4 is subsequently redistributed kinetochores (metaphase anaphase), midzone cleavage furrow formation (anaphase telophase), midbody (cytokinesis) cycle, required for division. Inhibition of PLK4 activity prevents cytokinesis, leading polyploidy vulnerability anaphase or mitotic catastrophe. The role in...
3082 Background: CLDN6, a member of the claudin family tight junction proteins, is expressed at high levels in multiple human malignancies and has little to no expression normal tissues. This profile makes CLDN6 an ideal target for development new therapeutics. TORL-1-23 first-in-class ADC targeting tumor-specific antigen CLDN6. Methods: TORL123-001 (NCT05103683) ongoing, 2-part, first study characterize safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD),...
Abstract Purpose Various aberrations in the fibroblast growth factor receptor genes FGFR1 , FGFR2 and FGFR3 are found different cancers, including breast cancer (BC). This study analyzed impact of FGFR amplification on BC prognosis. Methods The included 894 patients. rates FGFR2, were evaluated tissue microarrays using fluorescence situ hybridization (FISH). Associations between these parameters prognosis multivariate Cox regression analyses. Results FISH was assessable 503 samples, 447,...
CLDN6 is expressed at high levels in multiple cancers with little to no expression normal tissues and has been implicated the initiation, progression, metastasis of some cancers. an ideal target for development new therapeutics. TORL-1-23 first-in-class ADC targeting tumor-specific antigen CLDN6. This ongoing first human study (TORL123-001, NCT05103683) characterizes safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended phase 2 (RP2D) participants...
<p>Supplemental Figure S6: In vivo efficacy of a range doses CLDN6-23-ADC in M202 xenograft models. ADC dosing is IV QW as indicated by the arrows</p>
<p>Supplemental Figure S5: Induction of apoptosis following 48 hr treatment CLDN6 positive OVCA429 and negative M202 cells with a range concentrations (50 μg/ml - 0.3658μg/ml) CLDN6-23-ADC compared to control IgG ADC.</p>
<div>Abstract<p>Purpose: Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression normal adult tissue. This profile makes CLDN6 an ideal target for development of a potential therapeutic antibody-drug-conjugate (ADC). study describes the generation preclinical characterization CLDN6-23-ADC, ADC consisting humanized anti-CLDN6 monoclonal antibody coupled to MMAE via cleavable...
<p>Supplemental Figure S4: Binding of CLDN6-23-ADC (5 μg/ml) in artificial cell lines overexpressing CLDN3, CLDN4, CLDN6 or CLDN9 by flow cytometry.</p>
<p>Methods for Supplemental Data</p>
<p>File containing supplemental data</p>
<p>Supplemental Figure S7. CLDN6 expression in ovarian and endometrial cancer tissue samples.</p>
<p>Supplemental Figure S8. A. Layout of tissues and B. Scanned whole-slide image BN1021, normal human tissue microarray stained for CLDN6 expression showing no staining.</p>
<p>Supplemental Figure S3. A, Efficacy of anti-CLDN6 mouse antibodies in CLDN6 positive OV90 ovarian cancer cell line xenografts. B, UMUC4 bladder C, No efficacy negative M202 melanoma All are dosed at 10 mg/kg QW IV each study. Errors bars represent SEM 8 replicate animals per group.</p>
<p>Supplemental Figure S1: Expression of CLDN6 by transcript in the GTEX dataset normal tissue samples.</p>
<p>Supplemental Figure S2: Amino acid sequence alignment of CLDN6 (P56747) and CLDN9 (O95484) with the extracellular loops highlighted</p>
<p>Supplemental Figure S5: Induction of apoptosis following 48 hr treatment CLDN6 positive OVCA429 and negative M202 cells with a range concentrations (50 μg/ml - 0.3658μg/ml) CLDN6-23-ADC compared to control IgG ADC.</p>
<p>Supplemental Figure S3. A, Efficacy of anti-CLDN6 mouse antibodies in CLDN6 positive OV90 ovarian cancer cell line xenografts. B, UMUC4 bladder C, No efficacy negative M202 melanoma All are dosed at 10 mg/kg QW IV each study. Errors bars represent SEM 8 replicate animals per group.</p>
<p>Supplemental Figure S1: Expression of CLDN6 by transcript in the GTEX dataset normal tissue samples.</p>
<p>Supplemental Figure S6: In vivo efficacy of a range doses CLDN6-23-ADC in M202 xenograft models. ADC dosing is IV QW as indicated by the arrows</p>
<p>Supplemental Figure S8. A. Layout of tissues and B. Scanned whole-slide image BN1021, normal human tissue microarray stained for CLDN6 expression showing no staining.</p>