Folate receptor α: A storied past and promising future in immunotherapy

Folate receptor alpha (FRα) is a membrane-bound transport protein with several features which make it an attractive target for cancer immunotherapy. FRα is largely shielded from the immune system in normal tissue but exposed while expressed on a variety of malignancies; it is functionally active in cancer pathogenesis; and it is immunogenic. A variety of different immunotherapeutic methods targeting FRα are being explored to treat cancer. Passive immunotherapy includes monoclonal antibodies, antibodies modified to deliver treatments and modified T cell therapy. Active immunotherapy has focused on using FRα to increase the immunogenicity of cancer or to generate active FRα-directed immunity through a range of vaccination techniques. We will review the rationale behind targeting immunotherapy to FRα and cover the various techniques designed to do this. Folate Receptor alpha (FRα) is a unique tumor-associated antigen (TAA) with many characteristics that make it an attractive target for immunotherapy in cancer. Many different immunotherapeutic modalities utilizing FRα are being explored to treat cancer. The research is in various stages: some are just beyond conception, others have been tried and abandoned, and others still are progressing through human clinical trials. This review will cover immunotherapeutic methods, both active and passive, that target FRα.