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  1. Article: Novel Developments to Enable Treatment of CNS Diseases with Targeted Drug Delivery.

    Meyer, Axel H / Feldsien, Thomas M / Mezler, Mario / Untucht, Christopher / Venugopalan, Ramakrishna / Lefebvre, Didier R

    Pharmaceutics

    2023  Volume 15, Issue 4

    Abstract: The blood-brain barrier (BBB) is a major hurdle for the development of systemically delivered drugs against diseases of the central nervous system (CNS). Because of this barrier there is still a huge unmet need for the treatment of these diseases, ... ...

    Abstract The blood-brain barrier (BBB) is a major hurdle for the development of systemically delivered drugs against diseases of the central nervous system (CNS). Because of this barrier there is still a huge unmet need for the treatment of these diseases, despite years of research efforts across the pharmaceutical industry. Novel therapeutic entities, such as gene therapy and degradomers, have become increasingly popular in recent years, but have not been the focus for CNS indications so far. To unfold their full potential for the treatment of CNS diseases, these therapeutic entities will most likely have to rely on innovative delivery technologies. Here we will describe and assess approaches, both invasive and non-invasive, that can enable, or at least increase, the probability of a successful drug development of such novel therapeutics for CNS indications.
    Language English
    Publishing date 2023-03-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15041100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Convection enhanced delivery of EGFR targeting antibody-drug conjugates Serclutamab talirine and Depatux-M in glioblastoma patient-derived xenografts.

    Porath, Kendra A / Regan, Michael S / Griffith, Jessica I / Jain, Sonia / Stopka, Sylwia A / Burgenske, Danielle M / Bakken, Katrina K / Carlson, Brett L / Decker, Paul A / Vaubel, Rachael A / Dragojevic, Sonja / Mladek, Ann C / Connors, Margaret A / Hu, Zeng / He, Lihong / Kitange, Gaspar J / Gupta, Shiv K / Feldsien, Thomas M / Lefebvre, Didier R /
    Agar, Nathalie Y R / Eckel-Passow, Jeanette E / Reilly, Edward B / Elmquist, William F / Sarkaria, Jann N

    Neuro-oncology advances

    2022  Volume 4, Issue 1, Page(s) vdac130

    Abstract: Background: EGFR targeting antibody-drug conjugates (ADCs) are highly effective against EGFR-amplified tumors, but poor distribution across the blood-brain barrier (BBB) limits their efficacy in glioblastoma (GBM) when administered systemically. We ... ...

    Abstract Background: EGFR targeting antibody-drug conjugates (ADCs) are highly effective against EGFR-amplified tumors, but poor distribution across the blood-brain barrier (BBB) limits their efficacy in glioblastoma (GBM) when administered systemically. We studied whether convection-enhanced delivery (CED) can be used to safely infuse ADCs into orthotopic patient-derived xenograft (PDX) models of EGFRvIII mutant GBM.
    Methods: The efficacy of the EGFR-targeted ADCs depatuxizumab mafodotin (Depatux-M) and Serclutamab talirine (Ser-T) was evaluated
    Results: Dose-finding studies in orthotopic GBM6 identified single infusion of 2 μg Ser-T and 60 μg Depatux-M as safe and effective associated with extended survival prolongation (>300 days and 95 days, respectively). However, with serial infusions every 21 days, four Ser-T doses controlled tumor growth but was associated with lethal toxicity approximately 7 days after the final infusion. Limiting dosing to two infusions in GBM108 provided profound median survival extension of over 200 days. In contrast, four Depatux-M CED doses were well tolerated and significantly extended survival in both GBM6 (158 days) and GBM108 (310 days). In a toxicity analysis, Ser-T resulted in a profound loss in NeuN+ cells and markedly elevated GFAP staining, while Depatux-M was associated only with modest elevation in GFAP staining.
    Conclusion: CED of Depatux-M is well tolerated and results in extended survival in orthotopic GBM PDXs. In contrast, CED of Ser-T was associated with a much narrower therapeutic window.
    Language English
    Publishing date 2022-08-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 3009682-0
    ISSN 2632-2498 ; 2632-2498
    ISSN (online) 2632-2498
    ISSN 2632-2498
    DOI 10.1093/noajnl/vdac130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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