A5022150086- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Cancer Treatment and Pharmacology
- Biosimilars and Bioanalytical Methods
- Angiogenesis and VEGF in Cancer
- Protein Degradation and Inhibitors
- Synthesis and Biological Evaluation
- Synthesis and pharmacology of benzodiazepine derivatives
- Glycosylation and Glycoproteins Research
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Estrogen and related hormone effects
- Synthesis and properties of polymers
- Cancer, Hypoxia, and Metabolism
- RNA regulation and disease
- Cancer therapeutics and mechanisms
- Nanofabrication and Lithography Techniques
- Protein purification and stability
University of California, San Francisco
2002-2023
GTx (United States)
2022
Roche (Switzerland)
2021
Translational Research in Oncology
2006-2018
Genentech
2006-2013
Hull York Medical School
2012-2013
University of York
2012-2013
Leeds Teaching Hospitals NHS Trust
2013
Weatherford College
2010
Bipar
2001
Abstract We have developed a whole-mount immunocytochemical method for Xenopus and used it to map the expression of intermediate filament protein vimentin during early embryogenesis. two monoclonal antibodies, 14h7 RV202. Both label filaments in A6 cells. RV202 reacts specifically with (Mr, 55×103) on Western blots cells embryos. second, insoluble polypeptide 57×103Afr found The 57 ×103Afr appears be an immunochemically related vimentin. In embryo, we first at time neural tube closure (stage...
Antibody-drug conjugates (ADC), potent cytotoxic drugs covalently linked to antibodies via chemical linkers, provide a means increase the effectiveness of chemotherapy by targeting drug neoplastic cells while reducing side effects. Here, we systematically examine potential targets and linker-drug combinations that could an optimal ADC for treatment non-Hodgkin's lymphoma. We identified seven antigens (CD19, CD20, CD21, CD22, CD72, CD79b, CD180) lymphoma with ADCs. ADCs cleavable linkers...
Cancer stem cells (CSCs) are hypothesized to actively maintain tumors similarly how their normal counterparts replenish differentiated cell types within tissues, making them an attractive therapeutic target for the treatment of cancer. Because most CSC markers also label tissue cells, it is unclear selectively without compromising homeostasis. We evaluated a strategy that targets surface leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), well-characterized and marker, with...
Abstract Clinical results from the latest strategies for T-cell activation in cancer have fired interest combination immunotherapies that can fully engage immunity. In this study, we describe a trastuzumab-based bispecific antibody, HER2-TDB, which targets HER2 and conditionally activates T cells. HER2-TDB specifically killed HER2-expressing cells at low picomolar concentrations. Because of its unique mechanism action, is independent signaling or chemotherapeutic sensitivity, eliminated...
We are interested in identifying mechanisms of resistance to the current generation antibody-drug conjugates (ADC) and developing ADCs that can overcome this resistance.Pinatuzumab vedotin (anti-CD22-vc-MMAE) polatuzumab (anti-CD79b-vc-MMAE) contain microtubule inhibitor monomethyl auristatin E (MMAE) attached antibody by protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl (MC-vc-PAB). Early clinical trial data suggest these have promising efficacy for...
Antibody-drug conjugates (ADC) are designed to selectively bind tumor antigens via the antibody and release their cytotoxic payload upon internalization. Controllable through judicious design of linker has been an early technological milestone. Here, we examine effect protease-cleavable valine-citrulline [VC(S)] on ADC efficacy. The VC(S) was be cleaved by cathepsin B, a lysosomal cysteine protease. Surprisingly, suppression B expression CRISPR-Cas9 gene deletion or shRNA knockdown had no...
The antibody-drug conjugate (ADC) is a well-validated modality for the cell-specific delivery of small molecules with impact expanding rapidly beyond their originally-intended purpose treating cancer. However, antibody-mediated (AMD) remains inefficient, limiting its applicability to targeting highly potent payloads cells high antigen expression. Maximizing number delivered per antibody one key way in which efficiency can be improved, although this has been challenging carry out; few...
Abstract CD20 is an established therapeutic target in B-cell malignancies. The × CD3 bispecific antibody mosunetuzumab has significant efficacy non-Hodgkin lymphomas (NHLs). Because antigen loss a recognized mechanism of resistance, we evaluated expression relative to clinical response patients with relapsed and/or refractory NHL the phase 1/2 GO29781 trial investigating monotherapy. was studied using immunohistochemistry (IHC), RNA sequencing, and whole-exome sequencing performed centrally...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe mechanism of adenosine to inosine conversion by the double-stranded RNA unwinding/modifying activity: a high-performance liquid chromatography-mass spectrometry analysisAndrew G. Polson, Pamela F. Crain, Steven C. Pomerantz, James A. McCloskey, and Brenda L. BassCite this: Biochemistry 1991, 30, 49, 11507–11514Publication Date (Print):December 10, 1991Publication History Published online1 May 2002Published inissue 10 December...
ABSTRACT We have used whole-mount immunofluorescence mi-croscopy of late-stage Xenopus laevis oocytes and early embryos to examine the organization their cortical cytokeratin systems. In both mature embryos, there is a distinct animal-vegetal polarity in organization. (stage-VI) oocytes, filaments vegetal region form unique, almost geodesic net-work; animal region, appears much more variable irregular. unfer-tilized, postgerminal vesicle breakdown eggs, cor-tical system disorganized...
A new family of Ig domain receptors referred to as the immune receptor translocation-associated (IRTA) proteins, FcR homologs (FcRHs) or FcR-like that are expressed in lymphoid cells has been recently described. RNA expression analysis suggests FcRH1–5/IRTA1–5 exclusively subsets B-cell compartment. We generated mAbs and examined their protein pattern normal tissue chronic lymphocytic leukemia (CLL) cells. Our data indicated were sub-populations; however, some cases, was not same populations...
Fc receptor-like 5 (FcRL5/FcRH5/IRTA2/CD307) is a surface protein expressed selectively on B cells and plasma cells. We found that FcRL5 was at elevated levels the of from bone marrow patients diagnosed with multiple myeloma. This prevalence in myeloma narrow pattern normal expression indicate could be target for antibody-based therapies myeloma, particularly antibody-drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via specialized chemical linkers, where limited tissues...
Antibody-drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via chemical linkers, allow specific targeting of neoplastic cells. We have used this technology develop the ADC DCDT2980S that targets CD22, an antigen with expression limited B cells and vast majority non-Hodgkin lymphomas (NHL). consists a humanized anti-CD22 monoclonal IgG1 antibody microtubule-disrupting agent, monomethyl auristatin E (MMAE), reduced cysteines protease cleavable linker,...
A novel disulfide linker was designed to enable a direct connection between cytotoxic pyrrolobenzodiazepine (PBD) drugs and the cysteine on targeting antibody for use in antibody-drug conjugates (ADCs). ADCs composed of cysteine-engineered were armed with PBD using self-immolative linker. Both chemical site optimized this new bioconjugation strategy provide highly stable efficacious ADC. This ADC compared conjugate containing same drug, but attached via peptide had similar efficacy mice...
The treatment of patients with relapsed or refractory lymphoid neoplasms represents a significant clinical challenge. Here, we identify the pro-survival BCL-2 protein family member MCL-1 as resistance factor for inhibitor venetoclax in non-Hodgkin lymphoma (NHL) cell lines and primary NHL samples. Mechanistically, show that antibody-drug conjugate polatuzumab vedotin promotes degradation via ubiquitin/proteasome system. This targeted antagonism, when combined anti-CD20 antibodies...
The treatment of acute myeloid leukemia (AML) has not significantly changed in 40 years. Cytarabine- and anthracycline-based chemotherapy induction regimens (7 + 3) remain the standard care, most patients have poor long-term survival. reapproval Mylotarg, an anti-CD33-calicheamicin antibody-drug conjugate (ADC), demonstrated ADCs as a clinically validated option to enhance effectiveness therapy. We are interested developing next-generation ADC for AML improve upon initial success...
B7-H4 has been implicated in cancers of the female reproductive system and investigated for its possible use as a biomarker cancer, but there are no preclinical studies to demonstrate that is molecular target therapeutic intervention cancer. We provide evidence prevalence expression levels high different subtypes breast cancer only few normal tissues express on cell membrane. These profiles low upregulation an opportunity antibody–drug conjugates (ADCs), cytotoxic drugs chemically linked...