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Review
. 2024 Nov 1;35(6):494-498.
doi: 10.1097/ICU.0000000000001063. Epub 2024 May 30.

Ocular toxicities associated with antibody drug conjugates

Rayna F Marshall  1 , Hannah Xu  2 , Meghan Berkenstock  3
Affiliations
Review

Ocular toxicities associated with antibody drug conjugates

Rayna F Marshall et al. Curr Opin Ophthalmol. .

Abstract

Purpose of review: To review the structure, mechanism of action, and pathophysiology of antibody-drug conjugates (ADCs) used to treat gynecological malignancies associated with ocular adverse effects.

Recent findings: Recent research shows tisotumab vedotin causes ocular toxicity localized to the conjunctiva, with common adverse effects being conjunctivitis, dry eye, blepharitis, and keratitis. Toxicity is likely due to targeting tissue factor (TF) in the conjunctiva, leading to direct delivery of the cytotoxic payload resulting in apoptosis and bystander killing. Mirvetuximab soravtansine causes blurred vision, keratitis, or dry eye with toxicity often localized in the cornea. Off-target inflammation appears to cause ocular adverse effects, with nonreceptor mediated macropinocytosis by corneal stem cells.

Summary: Collaboration between oncologists and ophthalmologists with adherence to mitigation protocols can decrease the risk of ocular adverse events.

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References

    1. Tymon-Rosario J, Gorman M, Richardson DL, et al. Advances in antibody-drug conjugates for gynecologic malignancies. Curr Opin Obstet Gynecol 2023; 35:6–14.
    1. Turinetto M, Valsecchi AA, Tuninetti V, et al. Immunotherapy for cervical cancer: are we ready for prime time? Int J Mol Sci 2022; 23:3559.
    1. Bussing D, Li Z, Li Y, et al. Pharmacokinetics of monoclonal antibody and antibody fragments in the mouse eye following systemic administration. AAPS J 2021; 23:116.
    1. Moore KN, Martin LP, O’Malley DM, et al. A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer. Future Oncol 2018; 14:123–136.
    1. Dilawari A, Shah M, Ison G, et al. FDA approval summary: mirvetuximab soravtansine-gynx for FRα-positive, platinum-resistant ovarian cancer. Clin Cancer Res 2023; 29:3835–3840.

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