Cadonilimab (AK104) is a humanized tetravalent IgG1 bispecific antibody targeting PD1/CTLA4. Cadonilimab blocks both PD-1 and CTLA-4 pathways, thereby relieving their corresponding immunosuppressive effects and reversing tumor specific T cell exhaustion. Cadonilimab significantly downregulates Fc-mediated effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC). Cadonilimab can be used for research of metastatic cervical cancer, as well as other malignancies such as gastric cancer, GEJ adenocarcinoma and non-small cell lung cancer (NSCLC).
Cadonilimab (0-100 nM, 10-120 min) maintains a high affinity for Jurkat-CTLA4 and Jurkat-PD1 cells in vitro after iodine modification[4].
Cadonilimab (3.7 MBq, tail i.v., a single dose) modified with 124I largely enriches in the spleen, tumor sites and results in enrichment of PD1/CTLA4 positive immune cells at the tumor sites in humanized mice with MC38-hPD-L1 cell xenografts[4].
References:
[1]. Antonarelli G, et al. Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies. Pharmaceuticals (Basel). 2021 Aug 31;14(9):884.
[2]. Kaplon H, et al. Antibodies to watch in 2022. MAbs. 2022 Jan-Dec;14(1):2014296.
[3]. Chen PY, et al. Case Report: Cadonilimab-related toxic epidermal necrolysis-like reactions successfully treated with supplemental Adalimumab. Front Immunol. 2023 Aug 3;14:1188523.
[4]. Hou X, et al. Preclinical imaging evaluation of a bispecific antibody targeting hPD1/CTLA4 using humanized mice. Biomed Pharmacother. 2024 Jun;175:116669.