A5034390741- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Inflammatory mediators and NSAID effects
- Glycosylation and Glycoproteins Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthesis and biological activity
- Chemical Reactions and Isotopes
- Estrogen and related hormone effects
- Crystallography and molecular interactions
- Neuroendocrine Tumor Research Advances
- Advanced biosensing and bioanalysis techniques
- Ovarian cancer diagnosis and treatment
- HER2/EGFR in Cancer Research
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- Synthesis of Tetrazole Derivatives
- Phagocytosis and Immune Regulation
- Advanced Biosensing Techniques and Applications
- Click Chemistry and Applications
- Cancer therapeutics and mechanisms
- Fluorine in Organic Chemistry
Memorial Sloan Kettering Cancer Center
2016-2023
Hunter College
2016-2021
City University of New York
2016-2021
University of Alberta
2011-2016
Kettering University
2016
The Graduate Center, CUNY
2016
Cancer Institute (WIA)
2014
Abstract The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T; SC16LD6.5) is first-in-class DLL3-targeted antibody–drug conjugate with encouraging initial safety efficacy profiles SCLC the clinic. Here we demonstrate that tumor expression of DLL3, although orders magnitude lower surface protein than typical oncology targets immunoPET, can serve an imaging biomarker...
Abstract Human epidermal growth factor receptor 2 (HER2) gene amplification and/or protein overexpression in tumors is a prerequisite for initiation of trastuzumab therapy. Although HER2 cell membrane receptor, differential rates endocytosis and recycling engender dynamic surface pool HER2. Since must bind to the extracellular domain HER2, depressed hinders binding. Using vivo biological models cultures fresh human tumors, we find that caveolin-1 (CAV1) involved dynamics within context...
A critical benchmark in the development of antibody-based therapeutics is demonstration efficacy preclinical mouse models human disease, many which rely on immunodeficient mice. However, relatively little known about how biology various strains impacts vivo fate these drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric, and murine mAbs against four therapeutic oncologic targets to interrogate their biodistribution different mice bearing lung, prostate, ovarian cancer...
Abstract Purpose: Small cell lung cancer (SCLC) is an exceptionally lethal form of with limited treatment options. Delta-like ligand 3 (DLL3) attractive therapeutic target as surface expression almost exclusive to tumor cells. Experimental Design: We radiolabeled the anti-DLL3 mAb SC16 radioisotope, Lutetium-177. [177Lu]Lu-DTPA-CHX-A”-SC16 binds DLL3 on SCLC cells and delivers targeted radiotherapy while minimizing radiation healthy tissue. Results: demonstrated high uptake DLL3-target...
Abstract Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression governed by the androgen receptor (AR). AR central oncogenic driver of cancer (PCa) and also key regulator DNA repair in cancer. We report an innovative therapeutic strategy that exploits hormone-DNA circuit to enable molecularly-specific alpha particle irradiation PCa. Alpha-particle PCa prompted molecularly specific-targeting internalization humanized monoclonal antibody hu11B6 targeting hK2 further...
Antibodies are promising vectors for PET imaging. However, the high uptake of radioimmunoconjugates in nontarget tissues such as liver and spleen hampers their performance radiotracers. This off-target can lead to suboptimal tumor–to–background activity concentration ratios, decreasing contrast images reducing diagnostic utility. A possible cause this is sequestration by immune cells bearing Fc-γ-receptors (FcγR) that bind Fc regions antibodies. <b>Methods:</b> Since heavy chain glycans...
Rationale: The overwhelming majority of radioimmunoconjugates are produced via random conjugation methods predicated on attaching bifunctional chelators to the lysines antibodies. However, this approach inevitably produces poorly defined and heterogeneous immunoconjugates because antibodies have several distributed throughout their structure. To circumvent issue, we previously developed a chemoenzymatic bioconjugation strategy that site-specifically appends cargoes biantennary heavy chain...
Immuno-PET using desferrioxamine (DFO)-conjugated zirconium-89 ([
The conjugation of antibodies with cytotoxic drugs can alter their in vivo pharmacokinetics. As a result, the careful assessment behavior, and specifically tumor-targeting properties, antibody–drug conjugates represents crucial step development. In order to facilitate this process, we have created methodology that facilitates dual labeling an antibody both toxin radionuclide for positron emission tomography (PET). To minimize impact these modifications, chemoenzymatic approach leverages...
Advances in our understanding of the contribution aberrant glycosylation to pro-oncogenic signaling and metastasis tumor cells have reinvigorated development mucin-targeted therapies. Here, we validate tumor-targeting ability a novel monoclonal antibody (mAb), AR9.6, that binds MUC16 abrogates downstream oncogenic confer therapeutic response.The vitro ex vivo validation binding AR9.6 was achieved via flow cytometry, radioligand assay (RBA), immunohistochemistry (IHC). The targeting validated...
Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1-LOXL4, are copper-dependent enzymes that can modify proteins extracellular matrix. Expression LOX is elevated in many human cancers, including breast cancer. expression correlates with level tissue hypoxia, it known to play a critical role cancer metastasis. The goal present study was target (1) molecular probe fluorescent labeling visualize vitro (2) radiolabeled peptide vivo three different...
The elevation of cancer antigen 125 (CA125) levels in the serum asymptomatic patients precedes radiologic detection high-grade serous ovarian by at least 2 mo and final clinical diagnosis 5 mo. PET imaging CA125 expression cells may enhance evaluation extent disease provide a roadmap to surgery as well detect recurrence metastases. <b>Methods:</b><sup>89</sup>Zr-labeled mAb-B43.13 was synthesized target evaluated via biodistribution studies mice bearing OVCAR3 human adenocarcinoma...
Cyclooxygenase (COX) is the key enzyme within complex conversion of arachidonic acid into prostaglandins (PGs). Inhibitors this represent a particularly promising class compounds for chemoprevention and cancer therapy. The experimental data on involvement COX isoform COX-2 in tumour development progression, as well observed overexpression variety human cancers provide rationale targeting molecular imaging therapy cancer. A series trifluoromethyl-substituted pyrimidines was prepared novel...
The impact of androgen receptor (AR) activity in breast cancer biology is unclear. We characterized and tested a novel therapy to an AR-governed target cancer.Experimental Design: evaluated the expression prototypical AR gene products human kallikrein 2 (hK2) PSA models. screened 13 well-characterized cell lines for hK2 production upon vitro hormone stimulation by testosterone [dihydrotestosterone (DHT)]. AR-positive were further exposure estrogen (17β-Estradiol) synthetic progestin...
Epithelial ovarian cancer (EOC) is characterized by the overexpression of antigen 125 (CA125), a mucinous glycoprotein that serves as tumor biomarker. Early diagnosis EOC plagued its asymptomatic nature progression and limitations currently used immunoassay techniques detect CA125 shed in serum samples. Presently, there no technique available for vivo evaluation expression malignant tissues. Moreover, could be an unexplored pathophysiological time window detection EOC, during which it...