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    Home > Medical News > Latest Medical News > Suitable for a wide range of tumor types, innovative peptide-conjugated drugs to enhance the effect of immunotherapy

    Suitable for a wide range of tumor types, innovative peptide-conjugated drugs to enhance the effect of immunotherapy

    • Last Update: 2021-10-22
    • Source: Internet
    • Author: User
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    Cybrexa Therapeutics today announced that preclinical cancer models have demonstrated that the peptide-conjugated drug (PDC) CBX-12 under development can enhance the effectiveness of immune checkpoint inhibitors
    Currently, Cybrexa is conducting a Phase 1/2 clinical trial to determine the tolerability and safety of CBX-12

    The company’s initial focus will be on patients with ovarian cancer and small cell lung cancer (SCLC) overexpressing HER2


    Point inhibitors combined with chemotherapy are standard treatments for many solid tumors, but bone marrow suppression associated with chemotherapy can reduce the efficacy of immunotherapy
    Moreover, due to its influence on normal cells, chemotherapy will also produce various toxic side effects

    Targeted chemotherapy, such as antibody-conjugated drugs (ADC), is limited to the treatment of tumors that express high levels of target antigens


    So, is there any way to specifically target a wide range of tumor types while avoiding toxicity?

    One of the characteristics of all tumors is the acidic microenvironment
    CBX-12 can deliver a potent cytotoxin exatecan specifically to cells in a low pH environment

    It uses a unique variant of a low pH insertion peptide (pHLIP).
    The low pH changes the conformation of this peptide to deliver exatecan into the cell


    This selective targeting of tumor cells' mechanism of action avoids the toxicity associated with the therapy's attack on healthy cells
    Preclinical cancer models show that CBX-12 does not induce bone marrow suppression like chemotherapy


    ▲The mechanism of using low pH insert peptides to deliver anti-cancer drugs to tumor cells (picture source: Cybrexa official website)

    The researchers used a mouse model of colorectal cancer to further evaluate the effect of CBX-12 on the efficacy of PD-1 and CTLA4 immune checkpoint inhibitors
    Experimental results showed that compared with mice that received immune checkpoint inhibitors alone, mice treated with the combination therapy significantly delayed tumor growth, improved survival, and showed complete tumor regression

    Specifically, the combination of CBX-12 and PD-1 inhibitors delayed tumor growth in mice by 4 times, and the combination of CTLA4 inhibitors delayed tumor growth by 10 times


    Not only that, but mice that experienced complete tumor regression also showed long-term immune memory
    Injecting CBX-12-treated tumor cells into mice can cause an anti-tumor immune response, indicating that CBX-12 induces immunogenic cell death


    Gayle also pointed out that since the experiments are carried out in preclinical models, additional studies are needed in the future to understand the impact of this combination therapy on patients


    Reference materials:

    [1] A peptide-drug conjugate that targets the acidic environment of cancer cells may improve the efficacy of immunotherapy.
    Retrieved October 7, 2021, from https:// Yale spinout shows how targeting cancer cells' acidic environment might enhance immunotherapy.
    Retrieved October 7, 2021, from https:// environment-might-enhance-immunotherapy

    (The original text has been deleted)

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