Modakafusp alfa (TAK-573) is a humanized, anti-CD38 IgG4 monoclonal antibody fused to 2 attenuated IFNα2b molecules, which delivers interferon-alpha to CD38-expressing cells. Modakafusp alfa has direct anti-proliferative activity on multiple myeloma (MM) cancer cells in vitro and induces robust and durable antitumor responses in MM xenograft tumor models. Modakafusp alfa in combination with anti-PD-1 antibodies induces immunomodulation and antitumor responses with good tolerance in mice.
References:
[1]. Dan T. Vogl MD, et al. TAK-573, an Anti-CD38/Attenuated Ifnα Fusion Protein, Has Clinical Activity and Modulates the Ifnα Receptor (IFNAR) Pathway in Patients with Relapsed/Refractory Multiple Myeloma.Blood. 2020, 136 (1), 37-38. [2]. Fatholahi M, et al. TAK-573, an anti-CD38-targeted attenuated interferon alpha (IFNα) fusion protein, showed anti-myeloma tumor responses in combination with standard of care (SOC) agents in multiple myeloma (MM) xenograft tumor models in vivo[J]. Clinical Lymphoma, Myeloma and Leukemia, 2019, 19(10): e116. [3]. Hara T, et al. A murine reactive version of TAK-573 (anti-CD38 attenuated IFNα fusion protein) shows immunomodulatory and antitumor activity, alone and in combination with standard-of-care agents, in IFNa-insensitive, immunocompetent murine multiple myeloma tumor models[J]. Cancer Research, 2020, 80(16_Supplement): 5546-5546. [4]. Bruins W S C, et al. Modakafusp alfa (TAK-573), a novel CD38-targeting attenuated interferon-alpha immunocytokine, kills MM cells via NK cell activation[J]. Blood, 2022, 140(Supplement 1): 4236-4237.