Journal: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
The article is a narrative review of antibody–drug conjugates (ADCs) in gynecologic malignancies.
It explains ADC structure and mechanism (antibody targeting, linker stability, cytotoxic payload delivery), then summarizes current US-approved agents in gynecologic cancers:
- Mirvetuximab soravtansine (folate receptor-α–targeted) in ovarian cancer
- Tisotumab vedotin (Tissue Factor–targeted) in recurrent/metastatic cervical cancer
- Trastuzumab deruxtecan (HER2-targeted) in select gynecologic tumors
The review highlights how these agents have changed treatment options in heavily pretreated, advanced disease and outlines ongoing efforts to improve ADC design. Areas of active investigation include:
- New antigen targets (e.g., cadherin‑6, B7‑H4)
- Alternative cytotoxic payloads and linker technologies
- Optimization of pharmacokinetics and bystander effect
- Integration with chemotherapy and immunotherapy
The authors stress that significant toxicities—particularly ocular events and pneumonitis—require specialized prevention and management strategies, which may limit broader use outside experienced centers.
Key unmet needs and research priorities discussed include:
- Defining predictive biomarkers for target expression and response
- Understanding and overcoming resistance mechanisms
- Determining safety of reusing the same target or payload later in the disease course
- Clarifying optimal sequencing and combinations with existing systemic therapies
Overall, the review positions ADCs as a rapidly evolving, high-impact class in gynecologic oncology, with substantial promise but important toxicity and biologic questions that must be addressed through ongoing clinical and translational research.