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    Home > Medical News > Latest Medical News > Roche terminates CD40 monoclonal antibody development and advances FAP-CD40 double antibody to phase I clinical

    Roche terminates CD40 monoclonal antibody development and advances FAP-CD40 double antibody to phase I clinical

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    Recently, Roche’s semi-annual report disclosed the latest pipeline.
    A bispecific antibody RG6189 (RO7300490) that targets FAP-CD40 has entered phase I clinical trials, and Roche has eliminated non-selective CD40 agonists from the pipeline.
    selicrelumab
    .

    The CD40 receptor on antigen-presenting cells (APC) plays a key role in regulating the immune response and triggering the adaptive immune response
    .


    CD40 agonists can enhance the activation of dendritic cells (DC) and the accompanying tumor-specific T cell activation, making this target a promising target in cancer immunotherapy (CIT)


    However, the extensive expression of CD40 caused dose-limiting side effects, such as cytokine release syndrome (CRS) and hepatotoxicity, as well as the extensive expression of CD40 receptors on hematopoietic and non-hematopoietic cells, resulting in sink effects.
    Agonistic anti-CD40 molecules exhibit a very short serum half-life, which limits the efficacy of CD40 antibodies
    .


    If CD40 agonism can be selectively targeted to tumor cells, these limitations can be overcome


    Therefore, Roche researchers developed a bispecific FAP-CD40 antibody RO7300490, which induces CD40 agonism only in the presence of fibroblast activation protein alpha (FAP), which is a specific expression in tumor stroma.
    Protease
    .


    The preclinical research data on this product has been published in the journal CLINICAL CANCER RESEARCH


    This bispecific antibody is a fully human Ig1 double antibody that contains two CD40 Fv regions


    In vitro experiments have shown that RO7300490 triggers effective FAP-dependent APC activation and DC activation leads to enhanced T cell activation


    Among 10 hud40tg mice carrying MC38-FAP, 8 induced rapid tumor elimination in the FAP-huCD40 double antibody high-dose group (13.


    In addition, studies have shown that the FAP-CD40 double antibody induces tumor growth inhibition in a pancreatic tumor model with low invasion and rich interstitial FAP expression


    In terms of safety, the FAP-CD40 double antibody high-dose group is well tolerated in insectivorous monkeys and will not cause CD40-related toxicity


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