Tisotumab vedotin is an antibody drug conjugate (ADC) targeting tissue factor (TF), formed by covalently linking a fully human monoclonal antibody (TF-011) against TF with the microtubule disruptor Monometll Auristatin E (MMAE) . Tisotumab vedotin has immunomodulatory and anti-tumor activities, and can be used in the study of advanced or metastatic solid tumors such as cervical cancer.
Tisotumab vedotin induces immunogenic cell death in tumor cells expressing TF, leading to the release of endoplasmic reticulum stress markers, ATP, and high mobility histone B1 (HMGB1)[1].Tisotumab vedotin induces anti-tumor activity through MMAE mediated cytotoxicity, Fc mediated antibody dependent cell phagocytosis (ADCP), and Fab mediated protease activated receptor 2 (PAR-2) signaling inhibition[2].
Tisotumab vedotin can cause immunogenic tumor cell death, promote activation of F4/80+ and CD11c+ innate immune cells, and recruit them into xenograft tumors[1].Tisotumab vedotin (2 mg/kg; once daily; 25 days) has anti-tumor activity in a mouse model of pancreatic cancer[4].
References:
[1]. Gray E, et al. Tisotumab vedotin shows immunomodulatory activity through induction of immunogenic cell deathJournal for ImmunoTherapy of Cancer 2020;8. [2]. Alley S C, et al. Tisotumab vedotin induces anti-tumor activity through MMAE-mediated, Fc-mediated, and Fab-mediated effector functions in vitro[J]. Cancer Research, 2019, 79(13_Supplement): 221-221. [3]. Luu K, et al. A review of the novel tissue factor antibody-drug conjugate: Tisotumab vedotin. J Oncol Pharm Pract. 2023 Mar;29(2):441-449.
[4]. Rubahamya B, et al. Clinical translation of antibody drug conjugate dosing in solid tumors from preclinical mouse data. Sci Adv. 2024 May 31;10(22):eadk1894.