Patients with ovarian cancer are often diagnosed late and prone to frequent relapse. Despite advances in surgery and chemotherapy, treatment resistance can leave clinicians with limited options. But a new generation of antibody-based therapies is offering renewed hope, combining precision targeting with immune activation and potent cytotoxic delivery. So far, anti-angiogenic drugs, PARP inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, polymer-drug conjugates, and dual-targeted nanomedicines are in the field.
Almost all antibody therapies in oncology are based on the IgG class. But researchers at King’s College London have developed a novel IgE-based immunotherapy known as MOv18 IgE. Unlike IgG, which circulates in the blood, IgE binds tightly to tissue-resident immune cells, especially macrophages, and plays a central role in allergic and parasitic responses.
In ovarian cancer, where the tumor microenvironment is notoriously immunosuppressive, MOv18 IgE works by re-educating tumor-associated macrophages. Their study revealed that this antibody can reverse the suppressive state of these macrophages, triggering them and surrounding T cells to attack the tumor. Early-phase clinical trials even reported tumor shrinkage in patients resistant to conventional therapies.
One of the most clinically validated targets is folate receptor alpha (FRα), expressed in up to 80% of epithelial ovarian cancers. Mirvetuximab soravtansine is the first ADC approved for platinum-resistant ovarian cancer with FRα expression. Besides killing tumor cells, the drug also induces autophagic cell death, a mechanism that may help bypass traditional drug resistance. When combined with other agents like topotecan or anti-VEGF therapies, its efficacy improves further, underscoring the synergy potential of ADCs.
Second-generation FRα ADCs are now in development, with rinatabart sesutecan (Rina-S) standing out. This investigational ADC has shown an impressive ORR of 55.6% in heavily pretreated patients, regardless of FRα expression levels, suggesting that the therapeutic window for FRα-targeted ADCs may be wider than previously thought. With Phase 3 trials underway, Rina-S could provide more patients with access to this targeted approach.
HER2, a target in breast and gastric cancers, is now emerging in ovarian cancer therapy. Innovent Biologics' IBI354, a HER2-targeting ADC linked to a camptothecin derivative, has demonstrated promising results, especially in patients with low HER2 expression (IHC 1+), a group often overlooked by existing HER2-targeted therapies.
In early studies, IBI354 achieved ORRs over 50% with a strong safety profile and minimal high-grade toxicity. With a Phase 3 trial underway in China, HER2 ADCs could soon broaden the therapeutic arsenal for platinum-resistant ovarian cancer (PROC).
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