Search Results

Now showing 1 - 5 of 5

Some of the metrics are blocked by your
consent settings
Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment
(2024-07-24)
Fine, Justyn
;
Meksiriporn, Bunyarit
;
Tan, Jiacheng
;
Spangler, Jamie B.
Antibody-based therapeutics constitute a rapidly growing class of pharmaceutical compounds. However, monoclonal antibodies, which specifically engage only one target, often lack the mechanistic intricacy to treat complex diseases. To expand the utility of antibody therapies, significant efforts have been invested in designing multispecific antibodies, which engage multiple targets using a single molecule. These efforts have culminated in remarkable translational progress, including nine US Food and Drug Administration–approved multispecific antibodies, with countless others in various stages of preclinical or clinical development. In this review, we discuss several categories of multispecific antibodies that have achieved clinical approval or shown promise in earlier stages of development. We focus on the molecular mechanisms used by multispecific antibodies and how these mechanisms inform their customized design and formulation. In particular, we discuss multispecific antibodies that target multiple disease markers, multiparatopic antibodies, and immune-interfacing antibodies. Overall, these innovative multispecific antibody designs are fueling exciting advances across the immunotherapeutic landscape.
Some of the metrics are blocked by your
consent settings
Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1
(2024-05-16)
Ludwig, Seth D.
;
Meksiriporn, Bunyarit
;
Tan, Jiacheng
;
Kureshi, Rakeeb
;
Mishra, Akhilesh
Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance. Here, we report the development of antibody fusion proteins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The complementary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell activation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic antibodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes.
Some of the metrics are blocked by your
consent settings
Analyze of the Model for Cancer Transmission
(2021-05-22)
Suvarnamani, Alongkot
;
Pongsumpun, Puntani
Cancer is a disease which dividing of abnormal cells cannot controlled and can invade nearby tissues. Cancer cells can also spread to other body organs. Moreover, we know that the genetic is a cause of cancer. So, we used SIR model (Susceptible-Infected-Recovered) for focusing on the mathematical model of cancer. We examined the dynamics of the disease and use dynamic analysis for analyzing the stability of the model. Then we found the equilibrium states and the basic reproductive number of the mathematical model of cancer. By the numerical simulations, the comparison of the parameters effect to the model, result, and conclusion are presented.
Some of the metrics are blocked by your
consent settings
Efficacy of nanodiamond–doxorubicin complexes on human breast adenocarcinoma cell lines
(2019-12-04)
Locharoenrat, Kitsakorn
This paper aims to demonstrate the efficacy of the immobilisation of the chemotherapy drug doxorubicin on nanodiamond platforms as a potential cancer therapy. This effective drug is experimentally fed into a human breast adenocarcinoma cell lines. Drug loading activity and cell viability are detected by spectrometer, microscopy, and MTT assay in this study at Biomedical Physics Research Unit, Department of Physics, Faculty of Science, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand between 1 Oct 2018 and 10 Jun 2019. Experimental results show that in the basic environment (pH = 8.0), the nanodiamond carboxylic group cooperated with the doxorubicin amino group to form a stable and non-covalent bond on nanodiamond surfaces served as a simple physical adsorption. In an acidic environment suitable to targeting the cancer cells, the nanodiamond carboxylic group ionised so that doxorubicin is effectively released. Doxorubicin therefore affirmatively absorbed into the cytoplasm and later into the nucleus. The significant finding of the study is that IC-50 equivalent to 0.40 mg/mL and viable nanodiamond–doxorubicin is a good candidate material for drug delivery.
Some of the metrics are blocked by your
consent settings
In silico identification and in vitro validation of nogalamycin N-oxide (NSC116555) as a potent anticancer compound against non–small-cell lung cancer cells
(2019-03-01)
Obounchoey, Phongphat
;
Tabtimmai, Lueacha
;
Suphakun, Praphasri
;
Thongkhao, Kannika
;
Eurtivong, Chatchakorn
The epidermal growth factor receptor (EGFR) was found to be overexpressed in several cancers, especially in lung cancers. Finding new effective drug against EGFR is the key to cancer treatment. In this study, the GOLD docking algorithm was used to virtually screen for novel human EGFR inhibitors from the NCI database. Thirty-four hit compounds were tested for EGFR-tyrosine kinase (TK) inhibition. Two potent compounds, 1-amino-4-(4-[4-amino-2-sulfophenyl]anilino)-9,10-dioxoanthracene-2-sulfonic acid (NSC125910), and nogalamycin N-oxide (NSC116555) were identified with IC <inf>50</inf> values against EGFR-TK comparable to gefitinib; 16.14 and 37.71 nM, respectively. However, only NSC116555 demonstrated cytotoxic effects against non–small-cell lung cancer, A549, shown in the cell cytotoxicity assay with an IC <inf>50</inf> of 0.19 + 0.01 µM, which was more potent than gefitinib. Furthermore, NSC116555 showed cytotoxicity against A549 via apoptosis in a dose-dependent manner.

KMITL

Browse

Filters

Settings

Sort By

Results per page

Search Results