Week 3, April 2025: Antibody Therapeutics in Ovarian Cancer: The Next Wave

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.

Rewiring Immunity with IgE Antibodies

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.

The ADC Era

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 as a Target

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).