A5019571545- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Gastric Cancer Management and Outcomes
- Immune Cell Function and Interaction
- Advanced Breast Cancer Therapies
- NF-κB Signaling Pathways
- Computational Drug Discovery Methods
- Estrogen and related hormone effects
- Cancer Treatment and Pharmacology
- Lymphoma Diagnosis and Treatment
- Cardiac electrophysiology and arrhythmias
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Viral Infections and Immunology Research
- Cardiovascular Effects of Exercise
- Cardiac Arrhythmias and Treatments
- Chemokine receptors and signaling
- Cardiomyopathy and Myosin Studies
- Immune Response and Inflammation
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Cardiac pacing and defibrillation studies
- Viral Infectious Diseases and Gene Expression in Insects
Rutgers, The State University of New Jersey
2019-2022
Pfizer (United States)
2012-2020
Rutgers Sexual and Reproductive Health and Rights
2019-2020
Pfizer (United Kingdom)
2011
Pathogenic variants in PKP2 (plakophilin-2) cause arrhythmogenic right ventricular cardiomyopathy, a disease characterized by life-threatening arrhythmias and progressive cardiomyopathy leading to heart failure. No effective medical therapy is available prevent or arrest the disease. We tested hypothesis that adeno-associated virus vector-mediated delivery of human
Abstract Antibody–drug conjugates (ADC) represent a promising therapeutic modality for the clinical management of cancer. We sought to develop novel ADC that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells (TIC), which comprise most aggressive cell population in tumor. optimized anti-5T4 (A1mcMMAF) by sulfydryl-based conjugation humanized A1 antibody tubulin inhibitor monomethylauristatin F (MMAF) via maleimidocaproyl linker. A1mcMMAF exhibited potent vivo antitumor...
Abstract The approval of ado-trastuzumab emtansine (T-DM1) in HER2+ metastatic breast cancer validated HER2 as a target for HER2-specific antibody–drug conjugates (ADC). Despite its demonstrated clinical efficacy, certain inherent properties within T-DM1 hamper this compound from achieving the full potential targeting HER2-expressing solid tumors with ADCs. Here, we detail discovery PF-06804103, an anti-HER2 ADC designed to have widened therapeutic window compared T-DM1. We utilized...
ABSTRACT Background Pathogenic variants in plakophilin-2 (PKP2) cause arrhythmogenic right ventricular cardiomyopathy (ARVC), a disease characterized by life-threatening arrhythmias and progressive leading to heart failure. No effective medical therapy is available prevent and/or arrest the disease. We tested hypothesis that AAV-mediated delivery of human PKP2 gene an adult mammalian deficient can progression significantly prolong survival. Methods Experiments were carried out using...
CD40 ligand (CD40L) mRNA stability is dependent on an activation-induced pathway that mediated by the binding complexes containing multifunctional RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1) to a 3' untranslated region of transcript. To understand relationship between regulated CD40L and requirement for variegated expression during T-dependent response, we engineered mouse lacking element (CD40LΔ5) asked how this mutation altered multiple aspects humoral immunity. We...
Abstract Antibody-drug conjugates (ADCs) have emerged as an important class of cancer therapeutics. The FDA approval Kadcyla (T-DM1), a single agent for treatment HER2-positive advanced metastatic breast cancer, was significant milestone in the field targeted therapy, first and only ADC solid tumors. Despite 3-month improvement over standard care median survival, almost all patients eventually became refractory to T-DM1. We identified several possible areas improvement: 1) potency T-DM1...
Abstract We have described a posttranscriptional pathway of induced mRNA stability that occurs at late times T cell activation and is engaged by the binding polypyrimidine tract-binding protein (PTBP1) complex to 3′UTR CD40L transcript. explored in vivo role this generating mouse bearing deletion element (termed CD40LΔ5) found Tfh cells harboring defect expressed approximately 60% WT CD40L. Importantly, decrease corresponded poorly elaborated germinal center (GC) response which included...
Abstract 5T4 (also known as TPBG) is a transmembrane, tumor-associated protein that rapidly internalizes. In preclinical models of NSCLC, was identified marker undifferentiated tumorigenic cells express properties tumor-initiating (TICs) and associated with highly proliferating (Ki67 positive) cell phenotype. addition, has been worse clinical outcome in NSCLC (Damelin et al, Cancer Res, 2011). We constructed an ADC humanized anti-5T4 Ab (A1) linked to the tubulin inhibitor...
Abstract Antibody-drug conjugates (ADCs) represent a promising therapeutic modality for the clinical management of cancer. We sought to develop novel ADC that targets 5T4 (TPBG), an oncofetal antigen expressed on tumor-initiating cells (TICs), which comprise most aggressive cell population in tumor. optimized anti-5T4 (A1mcMMAF) by sulfydryl-based conjugation humanized A1 antibody tubulin inhibitor monomethylauristatin F (MMAF) via maleimidocaproyl linker. A1mcMMAF exhibited potent vivo...
<p>In vitro cytotoxicity of PF-06804103 across a panel cancer cell lines.</p>
<p>ADC retention times by hydrophobic interaction chromatography (HIC).</p>
<p>Includes Supplementary Materials and Methods, Data Figure Legends</p>
<p>Immunohistochemical evaluation of HER2 expression in vivo cell line and patient-derived xenograft models.</p>
<div>Abstract<p>The approval of ado-trastuzumab emtansine (T-DM1) in HER2<sup>+</sup> metastatic breast cancer validated HER2 as a target for HER2-specific antibody–drug conjugates (ADC). Despite its demonstrated clinical efficacy, certain inherent properties within T-DM1 hamper this compound from achieving the full potential targeting HER2-expressing solid tumors with ADCs. Here, we detail discovery PF-06804103, an anti-HER2 ADC designed to have widened therapeutic...
<p>Effects of Systemic Administration Free Payload Compared with Conventional HER2-vc0101 on Indicators Bone Marrow Toxicity and Levels in Rats</p>
<p>Immunohistochemical evaluation of HER2 expression in vivo cell line and patient-derived xenograft models.</p>
<p>In vivo efficacy of site-specific anti-HER2 vc0101 4 DAR ADCs in N87 xenograft tumor model.</p>
<p>In vivo efficacy of site-specific anti-HER2 vc0101 4 DAR ADCs in N87 xenograft tumor model.</p>
<div>Abstract<p>The approval of ado-trastuzumab emtansine (T-DM1) in HER2<sup>+</sup> metastatic breast cancer validated HER2 as a target for HER2-specific antibody–drug conjugates (ADC). Despite its demonstrated clinical efficacy, certain inherent properties within T-DM1 hamper this compound from achieving the full potential targeting HER2-expressing solid tumors with ADCs. Here, we detail discovery PF-06804103, an anti-HER2 ADC designed to have widened therapeutic...
<p>Effects of a Conventional and Site-Specific Conjugate Targeting HER2 on Indicators Bone Marrow Toxicity Serum ADC/Payload Exposures in Rats</p>
<p>Conjugation of vc0101 does not alter anti-HER2 mAb binding.</p>
<p>Includes Supplementary Materials and Methods, Data Figure Legends</p>
<p>Effects of Systemic Administration Free Payload Compared with Conventional HER2-vc0101 on Indicators Bone Marrow Toxicity and Levels in Rats</p>