Folate-targeted immunotherapies: Passive and active strategies for cancer

Abstract

The glycoprotein FR alpha is a membrane-attached transport protein that is shielded from the immune system in healthy cells. However, it is upregulated in various malignancies, involved in cancer development and is also immunogenic. Furthermore, FR alpha is a tumor-associated antigen endowed with unique properties, thus rendering it a suitable target for immunotherapeutic development in cancer. Various anti- FR alpha immunotherapeutic strategies are thus currently being developed and clinically assessed for the treatment of various solid tumors. These approaches include passive anti-FR alpha immunotherapies, such as monoclonal antibodies, or active immunotherapies, such as CART, folate haptens and vaccines. In this review, we will explore the advances in the field of FR alpha-based immune therapies and discuss both their successes and shortcomings in the clinical setting.