Is MonoMethyl auristatin E toxic to humans as a drug carrier?

Yes. MonoMethyl auristatin E (MMAE) is a payload for antibody-drug conjugates (ADCs) and is commonly used in the development of ADC drugs (anti-tumor conjugates). It has been found that at least 16 ADCs that have entered clinical trials contain MMAE and are cytotoxic. MMAE is a potent microtubule inhibitor that binds to tubulin, blocks tubulin polymerization and inhibits microtubule formation, leading to disruption of mitotic spindle assembly and arrest of tumor cells in the M phase of the cell cycle, leading to apoptosis. To minimize toxicity and maximize efficacy, MMAE is conjugated to a monoclonal antibody specifically targeting the patient's tumor through a cleavable peptide linker. The linker is stable in the extracellular environment but is easily cleaved to release MMAE after target cells bind and internalize the ADC. However, MMAE can also be toxic to healthy cells. In addition, MMAE-based ADCs may produce neurotoxicity, with the main neurotoxicity being sensorimotor polyneuropathy. A higher incidence of peripheral neuropathy has been reported in ADCs containing MMAE as a payload.

References:

[1] Monomethyl Auristatin E[J]. Definitions, 2020. DOI:10.32388/hcrd1w.

[2] ZHIWEN FU . Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates[J]. iScience, 2023. DOI:10.1016/j.isci.2023.107778.

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