Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 26 for “"antibody-drug conjugate"”.
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Epiregulin as a Novel Target for Antibody-Drug Conjugate Development for the Treatment of Colorectal Cancer
<p>Antibody-drug conjugates (ADCs) are a fast-growing class of molecularly targeted therapies with 13 currently approved and over a 100 in clinical trials. ADCs consist of a monoclonal antibody (mAb) conjugated to a potent cytotoxic payload to selectively target tumor antigens highly expressed on …
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Characterizing ALCAM as an oncoprotein and immunotherapeutic target in neuroblastoma
… (3) exploiting these findings with a novel antibody-drug conjugate platform to avoid on-target, off-tumor toxicities. We generated inducible ALCAM knockdown cell lines using CRISPR inhibition and profiled the effects on neuroblastoma growth and survival using live-cell monitoring assays, …
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Metal Mediated Mechanisms of Drug Release
… reactions, and their applications in targeted drug delivery (Figure 1). The first project relates to the development of a palladium mediated bond-cleavage or “decaging” reaction which can cause a propargyl carbamate to decompose and release an amine. This was further developed by the …
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Metabolic vulnerability in HER2-positive Breast Cancer
… molecule kinase inhibitor (lapatinib) and an antibody-drug conjugate (trastuzumab emtansine), have significantly prolonged the overall survival of HER2-positive breast cancer patients. However, almost all patients develop resistance either from the beginning of therapy or with prolonged …
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Synthesis and biological evaluation of auristatin-F recombinant antibody-drug conjugates for cancer therapy
… as a contribution to the emerging field of antibody-drug conjugate (ADC) therapeutics, in which novel ADCs were generated and biologically evaluated for therapeutic potential and specificity towards cancer cells. SNAP-tag site-directed conjugation was employed in order to overcome the …
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Targeting the actin cytoskeleton in HER2+ metastatic cancer cells using a macrolide toxin
… B (MycB), as a potential warhead for a novel antibody drug conjugate (ADC) to target highly metastatic HER2+ breast and ovarian cancers. We found that MycB treatment of HER2+ breast (SKBR3, MDA-MB-453) and ovarian (SKOV3) cancer cells led to loss of viability (IC50 values ≤ 64 nM). Sub-lethal …
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Targeting the B-Cell Receptor in Diffuse Large B-Cell Lymphoma
… platforms. Next, I used the anti-CD79B antibody drug conjugate Polatuzumab-Vedotin (POLA-V) as a tool to study regulators of surface BCR. By combining drug CRISPR screens with surface-CD79B sorted screens, I uncovered both regulators of synergy and resistance to an important therapeutic …
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A NOVEL, RAS-INDEPENDENT ROLE FOR NF1 IN MICROTUBULE DYNAMICS AND DAMAGE REPAIR DICTATES SENSITIVITY TO T-DM1 IN HER2 POSITIVE BREAST CANCER.
… cancer cells to T-DM1, the first approved Antibody-drug conjugate (ADC) in breast cancer, through a novel, RAS-independent function on microtubular dynamics and repair. NF1 exhibits all biochemical properties of a bona fide MAP and specifically enhances intratubular repair. These results …
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The Mechanism of cGAMP Induced Antitumor Effect and Its Application in Treating Cancer and Antibody Generation
… toxicity. Chapter Four describes developing an antibody-drug conjugate (ADC) that links a STING agonist to antibodies targeting EGFR, prevalent in many cancers. This STING ADC activates various immune cells and promotes macrophage polarization within tumors. Chapter Five utilizes cGAMP as an …
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Studies Towards a Second-Generation Synthesis of the Aplyronines
… render the aplyronines ideal payloads for antibody-drug conjugates but their prohibitively low natural abundance calls for an efficient total synthesis to overcome the supply issue. This dissertation describes the efforts towards developing a second-generation Paterson synthesis of the …
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NF1 AS A REGULATOR OF CYTOSKELETON DYNAMICS AND BIOMARKER FOR DECISION-MAKING IN HER2-POSITIVE BREAST CANCER
… cells demonstrated exquisite sensitivity to the antibody-drug conjugate (ADC) trastuzumab emtansine (T-DM1). This hypersensitivity was specific to the mertansine MT-targeting component (DM1) since it was i) replicated by the naked payload but not the antibody alone; ii) absent with other ADCs …
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Targeting the Tumor Stroma Using a Monoclonal Antibody Platform Technology
… the discovery and validation of a monoclonal antibody that selectively binds to FAP. The lead antibody, B12, was identified from a naïve murine single-chain variable fragment antibody phage display library screened against recombinant human FAP. The heavy and light chains of B12 were cloned …
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Rationally designed aplyronine analogues for use in antibody-drug conjugates
… potency renders the aplyronines promising drug candidates. However, the scarcity and structural complexity of the aplyronines brings challenges in supplying material to enable these studies, and calls into question their viability as commercial targets. Based on structure–activity …
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biological treatment options of multiple myeloma
… T cells, T cell engaging bispecific antibodies, antibody-drug conjugates along with steroids, and immunomodulatory therapies. Bortezomib, Carfilzomib, and Ixazomib are examples of proteasome inhibitors. Bortezomib is the predominant choice in treatment regimens. The basic action of proteosome …
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The Development of Methods for Generating Fc-Conjugates and Antibody-Drug Conjugates
… and proteins, constitute a valuable class of drugs due to their high target specificity and their ability to modulate protein interactions (PPIs), which are often considered ‘undruggable’ by traditional small molecule drugs. Additionally, antibodies possess many beneficial characteristics, …
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The Development of Peroxide-Responsive Arylboronic Acids for Antibody-Drug Conjugates and Small-Molecule Prodrugs
… can be exploited for the targeted delivery of drugs. Section I of this thesis describes the design, synthesis, and evaluation of antibody-drug conjugates (ADCs) comprising arylboronic acid linkers, which give responsive drug release in the presence of the elevated hydrogen peroxide in cancer. …
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Design of smart linkers and their applications in controlled-release drug delivery systems
Antibody drug conjugates (ADC) represents an interesting strategy in tumour targeted therapy . The approach is based on the combination of the high affinity of an antibody towards its antigen and the high cytotoxicity of a drug, leading to a selective therapuetic agent with improved efficacy and …
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FROM ANTIBODY-DRUG CONJUGATES TO MASKED ANTIBODIES: BIOPHYSICAL INSIGHT FOR THE RATIONAL DESIGN OF FUTURE THERAPIES
… years and, during this time, many successful antibody scaffolds have been based on wild-type humanized and human sequences of the immunoglobulin G isotype 1 (IgG1) subclass. In the past, several mutations have been engineered into these scaffolds, to optimise biological/physical properties or …
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The Development of a Tumour-Responsive Format for Antibody Conjugates
Antibody-drug conjugates (ADCs) are an emerging class of targeted therapeutics which exploit the selectivity of monoclonal antibodies towards particular membrane receptors, to deliver potent cytotoxins to a desired cell type. A significant amount of research has been undertaken to improve the …
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