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  1. AU="Christine Hosselet"
  2. AU="A Kalyani"
  3. AU="Crewe, Bjørn Thomas"
  4. AU="Hart, Traver"
  5. TI=Reorganizing Cross Sectional Interventional Procedures Practice During the Coronavirus Disease COVID 19 Pandemic
  6. AU="Herbert H. Lindner"
  7. AU="Pei-Ying Hsieh"
  8. AU="Savchenko, Sergey S"
  9. AU="Kothe, Ullrich"
  10. AU="Bhosale, Santosh D"
  11. AU="Santamarina-Albertos, Alba"
  12. AU="Scott M. Riester"
  13. AU="A Zappa, Marco"
  14. AU=Panciani Pier Paolo
  15. AU="La Cascio, L"
  16. AU="Getsuwan, Songpon"

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  1. Artikel ; Online: Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates

    Renée Procopio-Melino / Frank W. Kotch / Amar S. Prashad / Jose M. Gomes / Wenge Wang / Bo Arve / Andrew Dawdy / Lawrence Chen / Justin Sperry / Christine Hosselet / Tao He / Ronald Kriz / Laura Lin / Kimberly Marquette / Lioudmila Tchistiakova / Will Somers / Jason C. Rouse / Xiaotian Zhong

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Band 11

    Abstract: Abstract Next-generation site-specific cysteine-based antibody–drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation requires complex full reduction and reoxidation ...

    Abstract Abstract Next-generation site-specific cysteine-based antibody–drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation requires complex full reduction and reoxidation processes, impacting product quality. To overcome this technical challenge, we developed a novel antibody manufacturing process through cysteine (Cys) metabolic engineering in Chinese hamster ovary cells implementing a unique cysteine-capping technology. This development enabled a direct conjugation of drugs after chemoselective-reduction with mild reductant tris(3-sulfonatophenyl)phosphine. This innovative platform produces clinical ADC products with superior quality through a simplified manufacturing process. This technology also has the potential to integrate Cys-based site-specific conjugation with other site-specific conjugation methodologies to develop multi-drug ADCs and exploit multi-mechanisms of action for effective cancer treatments.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 670
    Sprache Englisch
    Erscheinungsdatum 2022-05-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

    Sujiet Puthenveetil / Haiyin He / Frank Loganzo / Sylvia Musto / Jesse Teske / Michael Green / Xingzhi Tan / Christine Hosselet / Judy Lucas / L Nathan Tumey / Puja Sapra / Chakrapani Subramanyam / Christopher J O'Donnell / Edmund I Graziani

    PLoS ONE, Vol 12, Iss 5, p e

    2017  Band 0178452

    Abstract: Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads ... ...

    Abstract Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2017-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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