FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4324017838> ?p ?o ?g. }

• W4324017838 endingPage "e0282831" @default.
• W4324017838 startingPage "e0282831" @default.
• W4324017838 abstract "Imiquimod, a Toll-like receptor 7 (TLR7) agonist is routinely used for topical administration in basal cell carcinoma and stage zero melanoma. Similarly, the TLR agonist Bacillus Calmette-Guérin is used for the local treatment of bladder cancer and clinical trials showed treatment efficacy of intratumoral injections with TLR9 agonists. However, when administered systemically, endosomal TLR agonists cause adverse responses due to broad immune activation. Hence, strategies for targeted delivery of TLR agonists to the tumor tissue are needed to enable the widespread use of endosomal TLR agonists in the context of tumor immunotherapy. One strategy for targeted delivery of TLR agonist is their conjugation to tumor antigen-specific therapeutic antibodies. Such antibody-TLR agonist conjugates act synergistically by inducing local TLR-mediated innate immune activation which complements the anti-tumor immune mechanisms induced by the therapeutic antibody. In this study, we explored different conjugation strategies for TLR9 agonists to immunoglobulin G (IgG). We evaluated biochemical conjugation of immunostimulatory CpG oligodesoxyribonucleotides (ODN) to the HER2-specific therapeutic antibody Trastuzumab with different cross-linkers comparing stochastic with site-specific conjugation. The physiochemical make-up and biological activities of the generated Trastuzumab-ODN conjugates were characterized in vitro and demonstrated that site-specific conjugation of CpG ODN is crucial for maintaining the antigen-binding capabilities of Trastuzumab. Furthermore, site-specific conjugate was effective in promoting anti-tumor immune responses in vivo in a pseudo-metastasis mouse model with engineered human HER2-transgenic tumor cells. In this in vivo model, co-delivery of Trastuzumab and CpG ODN in form of site-specific conjugates was superior to co-injection of unconjugated Trastuzumab, CpG ODN or stochastic conjugate in promoting T cell activation and expansion. Thereby, this study highlights that site-specific conjugation of CpG ODN to therapeutic antibodies targeting tumor markers is a feasible and more reliable approach for generation of conjugates which retain and combine the functional properties of the adjuvant and the antibody." @default.
• W4324017838 created "2023-03-14" @default.
• W4324017838 creator A5024315469 @default.
• W4324017838 creator A5025344866 @default.
• W4324017838 creator A5050143061 @default.
• W4324017838 creator A5054414352 @default.
• W4324017838 creator A5073481924 @default.
• W4324017838 date "2023-03-13" @default.
• W4324017838 modified "2023-10-01" @default.
• W4324017838 title "Antibody conjugates for targeted delivery of Toll-like receptor 9 agonist to the tumor tissue" @default.
• W4324017838 cites W1504879144 @default.
• W4324017838 cites W1558949171 @default.
• W4324017838 cites W1571520647 @default.
• W4324017838 cites W1983386052 @default.
• W4324017838 cites W1992175481 @default.
• W4324017838 cites W1994447535 @default.
• W4324017838 cites W2005070267 @default.
• W4324017838 cites W2018939316 @default.
• W4324017838 cites W2025273503 @default.
• W4324017838 cites W2035035763 @default.
• W4324017838 cites W2035983102 @default.
• W4324017838 cites W2044757050 @default.
• W4324017838 cites W2046262584 @default.
• W4324017838 cites W2064839484 @default.
• W4324017838 cites W2066424312 @default.
• W4324017838 cites W2075119181 @default.
• W4324017838 cites W2083022271 @default.
• W4324017838 cites W2083868671 @default.
• W4324017838 cites W2105270641 @default.
• W4324017838 cites W2105687677 @default.
• W4324017838 cites W2116150122 @default.
• W4324017838 cites W2133105825 @default.
• W4324017838 cites W2137587451 @default.
• W4324017838 cites W2141021804 @default.
• W4324017838 cites W2152811375 @default.
• W4324017838 cites W2153746213 @default.
• W4324017838 cites W2162841866 @default.
• W4324017838 cites W2169149961 @default.
• W4324017838 cites W2191601131 @default.
• W4324017838 cites W2294193109 @default.
• W4324017838 cites W2305943786 @default.
• W4324017838 cites W2417431203 @default.
• W4324017838 cites W2463290481 @default.
• W4324017838 cites W2473214546 @default.
• W4324017838 cites W2528999955 @default.
• W4324017838 cites W2597045666 @default.
• W4324017838 cites W2612068032 @default.
• W4324017838 cites W2737785069 @default.
• W4324017838 cites W2767336874 @default.
• W4324017838 cites W2769124823 @default.
• W4324017838 cites W2783205443 @default.
• W4324017838 cites W2796938019 @default.
• W4324017838 cites W2801059620 @default.
• W4324017838 cites W2896033748 @default.
• W4324017838 cites W2905098668 @default.
• W4324017838 cites W2919411233 @default.
• W4324017838 cites W2922195937 @default.
• W4324017838 cites W2970782214 @default.
• W4324017838 cites W3111948793 @default.
• W4324017838 cites W3122174179 @default.
• W4324017838 cites W3131913078 @default.
• W4324017838 doi "https://doi.org/10.1371/journal.pone.0282831" @default.
• W4324017838 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36913398" @default.
• W4324017838 hasPublicationYear "2023" @default.
• W4324017838 type Work @default.
• W4324017838 citedByCount "0" @default.
• W4324017838 crossrefType "journal-article" @default.
• W4324017838 hasAuthorship W4324017838A5024315469 @default.
• W4324017838 hasAuthorship W4324017838A5025344866 @default.
• W4324017838 hasAuthorship W4324017838A5050143061 @default.
• W4324017838 hasAuthorship W4324017838A5054414352 @default.
• W4324017838 hasAuthorship W4324017838A5073481924 @default.
• W4324017838 hasBestOaLocation W43240178381 @default.
• W4324017838 hasConcept C104317684 @default.
• W4324017838 hasConcept C126322002 @default.
• W4324017838 hasConcept C150194340 @default.
• W4324017838 hasConcept C150903083 @default.
• W4324017838 hasConcept C159654299 @default.
• W4324017838 hasConcept C170493617 @default.
• W4324017838 hasConcept C190727270 @default.
• W4324017838 hasConcept C203014093 @default.
• W4324017838 hasConcept C207001950 @default.
• W4324017838 hasConcept C22801619 @default.
• W4324017838 hasConcept C2777701055 @default.
• W4324017838 hasConcept C2778938600 @default.
• W4324017838 hasConcept C2779138994 @default.
• W4324017838 hasConcept C2780674031 @default.
• W4324017838 hasConcept C502942594 @default.
• W4324017838 hasConcept C55493867 @default.
• W4324017838 hasConcept C71924100 @default.
• W4324017838 hasConcept C86803240 @default.
• W4324017838 hasConcept C8891405 @default.
• W4324017838 hasConcept C98274493 @default.
• W4324017838 hasConceptScore W4324017838C104317684 @default.
• W4324017838 hasConceptScore W4324017838C126322002 @default.
• W4324017838 hasConceptScore W4324017838C150194340 @default.
• W4324017838 hasConceptScore W4324017838C150903083 @default.
• W4324017838 hasConceptScore W4324017838C159654299 @default.

• next