Nature Medcine: The first CD70 mono-antitherapy for acute leukemia was effective, with 67% of patients completely remission.

Acute myeloid leukemia (AML) is a blood cancer with abnormal proliferation of myeloid leukocytes (but not lymphoid leukocytes).it is characterized by the rapid proliferation of abnormal cells in bone marrow, which affects the production of normal blood cells.AML is the most common acute leukemia in adults, and its incidence rate increases with age.leukemia stem cells (LSCs) that drive AML are usually resistant to conventional chemotherapy, so the relapse rate of AML is high.hypomethylated drugs (HMA) are the standard treatment for AML patients who are older or unsuitable for other therapies, but the response is moderate and does not last.cusatuzumab is the first anti-CD70 monoclonal antibody drug. CD70 is an immune checkpoint protein in blood cancer, some solid tumors and autoimmune diseases. Cusatuzumab can produce a variety of anticancer effects by binding with CD70, including blocking cd70-cd27 signal transduction, inhibiting the proliferation of leukemic stem cells, antibody dependent cytotoxicity, complement dependent cytotoxic effect and killing Death of CD70 expressing cancer cells, stimulation of tumor cell differentiation and death, and remodeling of immune system to monitor solid tumors.early clinical trials showed that cusatuzumab had good safety and tolerance to cutaneous T-cell carcinoma lymphoma and acute myeloid leukemia (AML), showing a certain anticancer effect.on June 30, 2020, researchers from the University of Bern in Switzerland published a research paper entitled "targeting CD70 with cusatuzumab eliminates acute myoid leukemia stem cells in patients treated with metabolic agents" in nature medicine, a top international medical journal.this study confirmed that leukemic stem cells (LSCs) upregulated CD70 expression during hypomethylation drug (HMA) treatment, resulting in increased CD70 / CD27 signal transduction, resulting in treatment resistance.the team used cusatuzumab (a human α - CD70 monoclonal antibody with enhanced antibody dependent cytotoxic effect) to target CD70 in leukemia stem cells (LSC) and block CD70 / CD27 signal transduction, which can clear leukemia stem cells (LSC) in vitro and xenotransplantation experiments.based on these preclinical results, the team conducted a phase 1 / 2 clinical trial in elderly patients with previously untreated acute myeloid leukemia (AML) treated with cusatuzumab monotherapy or in combination with azacytidine, a hypomethylated drug (HMA).of the 12 patients enrolled, 8 patients had complete remission (CR), 2 patients had complete remission (CRI), 2 patients had partial remission (PR), and the complete remission rate was 67%. The median response time was 3.3 months.and no dose limiting toxicity was found during the test.more importantly, cusatuzumab treatment significantly reduced leukemia stem cells (LSC) and triggered gene expression related to bone marrow differentiation and apoptosis.in general, cusatuzumab monotherapy and combination therapy with azacitidine, a hypomethylated drug, are effective in patients with acute myeloid leukemia (AML) who have not received intensive chemotherapy.cusatuzumab effectively eliminated CD70 expressing leukemia stem cells (LSCs), which may lead to deep and lasting remission.ongoing and ongoing phase 2 and phase 3 clinical trials will further study the potential of cusatuzumab combined with hypomethylated drugs (HMA) to induce sustained response and deep remission in more patients. cusatuzumab, an anti-CD70 monoclonal antibody drug developed by argenx company, is also the first anti-CD70 monoclonal antibody drug. In December 2018, cilag GmbH international, a subsidiary of Janssen Pharmaceutical companies, obtained the authorization of cusatuzumab (argx-110) with a huge amount of US $1.6 billion. mechanism of cusatuzumab: 1. Blocking cd70-cd27 signal transduction, leading to bone marrow differentiation and inhibiting the proliferation of leukemia stem cells; preventing the release of soluble CD27 (scd27) produced by cd70-cd27 junction; 2. Killing cancer cells through FC dependent complement dependent cytotoxicity (CDC) and enhancing antibody dependent cytotoxicity (ADCC). paper links: