We first generated a single-chain variable fragment derived from the anti-folate receptor α (FRα) antibody MORAb-003, then we engineered M13 bacteriophage displaying this targeting moiety, enabling high-affinity recognition of FRα-overexpressing ovarian cancer cells...The resulting M13FRα-Ce6-RB conjugates exhibit potent photodynamic activity under both red and green light irradiation, highlighting the potential of refactored M13 phages as flexible nanocarriers for precision phototherapy. This work presents a customizable and translationally relevant nanoplatform for image-guided treatment of chemoresistant ovarian cancer and other FRα-positive malignancies.

P1, N=1, Terminated, Instil Bio | N=51 --> 1 | Trial completion date: Nov 2039 --> Mar 2026 | Active, not recruiting --> Terminated; The study was terminated early due to discontinuation of development of the investigational program

The reduced dose FRα vaccine is as effective as the original dose and does not require CP to generate maximal immunity. These findings may inform the design of trials testing efficacy in TNBC or other cancers.

P1, N=4, Terminated, Novartis Pharmaceuticals | Trial completion date: Aug 2030 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2030 --> Jul 2025; Study termination based on sponsor decision due to lack of tolerability observed with [177Lu]Lu-EVS459

P1, N=33, Recruiting, Institute of Cancer Research, United Kingdom | Not yet recruiting --> Recruiting | Initiation date: May 2025 --> Aug 2025

MOv18 IgE retains monomeric purity in response to formulation and stress conditions, confirming stability. Our results offer crucial guidance for future IgE-based drug development.

P1, N=33, Not yet recruiting, Institute of Cancer Research, United Kingdom

We demonstrate that IgE induces hyperinflammatory repolarised states of patient-derived macrophages to inhibit Treg cell immunosuppression. These processes may collectively promote immune activation in ovarian cancer patients receiving IgE therapy.

Urticarial skin reactions following MOv18 IgE treatment were unlikely to result from allergic mechanisms or skin antigen recognition. The clinical presentation is consistent with infusion-related reactions commonly observed with monoclonal antibody treatments.

P1, N=4, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=96 --> 4

However, the treatment is associated with a high incidence of gastrointestinal and hematological AEs, raising the need for careful patient selection. Further studies are required to refine the therapeutic regimen and ensure an optimal balance between efficacy and safety.

We summarize the mechanisms of the action of various therapeutic strategies based on FRα, including MABs (monoclonal antibodies), ADCs (antibody-drug conjugates), FDCs (folate-drug conjugates), SMDCs (small molecule-drug conjugates), vaccines, and CAR-T (chimeric antigen receptor T) cells, and present the most significant clinical trials of some FRα-based drugs. Furthermore, we discuss the pros and cons of different FR-based therapies, highlighting mirvetuximab soravtansine (MIRV) as the currently most promising EOC-targeting drug.