FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2972431956> ?p ?o ?g. }

• W2972431956 abstract "Antibody-drug conjugates (ADCs) targeting the RON receptor, a tumorigenic factor contributing to cancer malignancy, has been considered as a novel strategy for cancer therapy. Here we describe a humanized antibody recognizing the RON plexin-semaphorin-integrin (PSI) domain with increased drug delivery capability for potential clinical application.Monoclonal antibody PCM5B14 specific to the human and monkey RON PSI domain was generated and characterized by various immunological methods. Humanized antibody H5B14 was created by grafting PCM5B14 complementarity-determining regions into human IgG1/κ acceptor frameworks and conjugated with monomethyl auristatin E and duocarmycin to form two H5B14-based ADCs. Stability of H5B14-based ADCs in human plasma was measured using hydrophobic interaction chromatography. Various biochemical and biological assays were used to determine ADC- regulated RON internalization, cell viability, spheroid formation, and death of cancer stem-like cells. Efficacies of H5B14-based ADCs in vivo were validated using tumor xenograft models. Maximal tolerated doses of H5B14-based ADCs were established in mice.H5B14 was highly specific to the human RON PSI domain and superior over other anti-RON ADCs in induction of RON internalization in various cancer cell lines tested. H5B14-based ADCS had a drug to antibody ratio of ~ 3.70:1 and were stable in human plasma with a minimal dissociation within a 10-day period. Functionally, H5B14-mediated drug delivery decreased cell viability at early stages with an average IC50 at ~ 20 nM in multiple cancer cell lines examined. H5B14-based ADCs also inhibited spheroid formation and caused death of cancer stem-like cells with RON+/CD44+/ESA+ phenotypes. In vivo, H5B14-based ADCs in a single injection inhibited tumor xenograft growth mediated by multiple cancer cell lines. Tumoristatic concentrations calculated from xenograft tumor models were in the range of 0.63 to 2.0 mg/kg bodyweight. Significantly, H5B14-based ADCs were capable of eradicating tumors at variable levels across multiple xenograft models regardless their malignant statuses. Toxicologically, H5B14-based ADCs were well tolerated in mice up to 60 mg/kg.H5B14-based ADCs targeting the RON PSI domain are superior in inducing RON internalization, leading to robust drug delivery and overall inhibition and eradication of tumors in multiple xenograft models. These findings warrant H5B14-based ADCs for clinical trials in the future." @default.
• W2972431956 created "2019-09-19" @default.
• W2972431956 creator A5003120776 @default.
• W2972431956 creator A5016279200 @default.
• W2972431956 creator A5032685651 @default.
• W2972431956 creator A5043666735 @default.
• W2972431956 creator A5048818909 @default.
• W2972431956 creator A5065491159 @default.
• W2972431956 creator A5067614647 @default.
• W2972431956 creator A5071860009 @default.
• W2972431956 creator A5084071156 @default.
• W2972431956 date "2019-09-13" @default.
• W2972431956 modified "2023-10-10" @default.
• W2972431956 title "Therapeutic efficacy of a novel humanized antibody-drug conjugate recognizing plexin-semaphorin-integrin domain in the RON receptor for targeted cancer therapy" @default.
• W2972431956 cites W1542053886 @default.
• W2972431956 cites W1749752941 @default.
• W2972431956 cites W1844728007 @default.
• W2972431956 cites W1963720869 @default.
• W2972431956 cites W1966828606 @default.
• W2972431956 cites W1983483937 @default.
• W2972431956 cites W1984101180 @default.
• W2972431956 cites W1997696802 @default.
• W2972431956 cites W2013878853 @default.
• W2972431956 cites W2019264784 @default.
• W2972431956 cites W2019291236 @default.
• W2972431956 cites W2031491298 @default.
• W2972431956 cites W2033247490 @default.
• W2972431956 cites W2035479572 @default.
• W2972431956 cites W2041799969 @default.
• W2972431956 cites W2048399755 @default.
• W2972431956 cites W2050738379 @default.
• W2972431956 cites W2078343277 @default.
• W2972431956 cites W2083285346 @default.
• W2972431956 cites W2087836279 @default.
• W2972431956 cites W2097644281 @default.
• W2972431956 cites W2102072877 @default.
• W2972431956 cites W2118942065 @default.
• W2972431956 cites W2124514746 @default.
• W2972431956 cites W2129875426 @default.
• W2972431956 cites W2137950260 @default.
• W2972431956 cites W2147525904 @default.
• W2972431956 cites W2160393730 @default.
• W2972431956 cites W2194390860 @default.
• W2972431956 cites W2287661813 @default.
• W2972431956 cites W2312309812 @default.
• W2972431956 cites W2336243671 @default.
• W2972431956 cites W2430472630 @default.
• W2972431956 cites W2513421068 @default.
• W2972431956 cites W2513494897 @default.
• W2972431956 cites W2742314046 @default.
• W2972431956 cites W2754341699 @default.
• W2972431956 cites W2795041486 @default.
• W2972431956 cites W2811379362 @default.
• W2972431956 cites W2894948154 @default.
• W2972431956 cites W2935573230 @default.
• W2972431956 cites W4236361077 @default.
• W2972431956 cites W62114904 @default.
• W2972431956 doi "https://doi.org/10.1186/s40425-019-0732-8" @default.
• W2972431956 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6743155" @default.
• W2972431956 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31519211" @default.
• W2972431956 hasPublicationYear "2019" @default.
• W2972431956 type Work @default.
• W2972431956 sameAs 2972431956 @default.
• W2972431956 citedByCount "16" @default.
• W2972431956 countsByYear W29724319562020 @default.
• W2972431956 countsByYear W29724319562021 @default.
• W2972431956 countsByYear W29724319562022 @default.
• W2972431956 crossrefType "journal-article" @default.
• W2972431956 hasAuthorship W2972431956A5003120776 @default.
• W2972431956 hasAuthorship W2972431956A5016279200 @default.
• W2972431956 hasAuthorship W2972431956A5032685651 @default.
• W2972431956 hasAuthorship W2972431956A5043666735 @default.
• W2972431956 hasAuthorship W2972431956A5048818909 @default.
• W2972431956 hasAuthorship W2972431956A5065491159 @default.
• W2972431956 hasAuthorship W2972431956A5067614647 @default.
• W2972431956 hasAuthorship W2972431956A5071860009 @default.
• W2972431956 hasAuthorship W2972431956A5084071156 @default.
• W2972431956 hasBestOaLocation W29724319561 @default.
• W2972431956 hasConcept C121608353 @default.
• W2972431956 hasConcept C126322002 @default.
• W2972431956 hasConcept C132538176 @default.
• W2972431956 hasConcept C139770010 @default.
• W2972431956 hasConcept C150903083 @default.
• W2972431956 hasConcept C159654299 @default.
• W2972431956 hasConcept C170493617 @default.
• W2972431956 hasConcept C203014093 @default.
• W2972431956 hasConcept C207001950 @default.
• W2972431956 hasConcept C2777092746 @default.
• W2972431956 hasConcept C2777325958 @default.
• W2972431956 hasConcept C502942594 @default.
• W2972431956 hasConcept C542903549 @default.
• W2972431956 hasConcept C71924100 @default.
• W2972431956 hasConcept C86803240 @default.
• W2972431956 hasConcept C96232424 @default.
• W2972431956 hasConcept C98274493 @default.
• W2972431956 hasConceptScore W2972431956C121608353 @default.
• W2972431956 hasConceptScore W2972431956C126322002 @default.
• W2972431956 hasConceptScore W2972431956C132538176 @default.
• W2972431956 hasConceptScore W2972431956C139770010 @default.
• W2972431956 hasConceptScore W2972431956C150903083 @default.

• next