ChemicalBook Product Catalog API Antineoplastic agents Other antineoplastic Drugs Tisotumab Vedotin

Tisotumab Vedotin

Product NameTisotumab Vedotin
CAS1418731-10-8
MF
MW0
EINECS
MOL FileMol File

Chemical Properties

form	Liquid
color	Colorless to light yellow

Usage And Synthesis

Uses

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 Monomethyll Auristatin E (MMAE) (HY-15162). 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[1][2][3].

Uses

Tisotumab Vedotin is an antibody-drug conjugate (ADC) designed to treat patients with relapsed or refractory cervical cancer.

Mechanism of action

Tisotumab Vedotin specifically binds to TF through its antibody portion, promoting the internalization of the drug in tumor cells, followed by the release of MMAE through a protease-cleavable linker, which exerts an anti-proliferative effect by blocking the polymerization of microtubules.

Side effects

Side effects of tisotumab vedotin may include eye inflammation, rash, nausea, fatigue, bleeding, and infection.

Synthesis

Tisotumab vedotin is present in a 4:1 linker-drug carrier to antibody ratio and may be synthesized in a manner similar to other ADCs using vedotin, such as Adcetris, Polivy, and Padcev. In these synthetic methods, the thiol group in 31.2 is exposed by reduction of the antibody disulfide bonds mediated by TCEP or DTT. Subsequently, the thiol group in 31.2 reacts with the maleimide linker functional group in 31.3 to generate Tisotumab vedotin 31, and any unreacted linker-drug carrier is quenched by using excess N-acetylcysteine.
Synthesis of Tisotumab Vedotin

in vivo

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].

Animal Model:	HPAF-II, SCID mice^[4].
Dosage:	2 mg/kg
Administration:	Once daily; 25 days
Result:	Decreased the tumor volume over the 3-week window.

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. DOI:10.1177/10781552221139775
[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. DOI:10.1126/sciadv.adk1894