Targeting folate receptor alpha for cancer treatment

Abstract

Promising targeted treatments and immunotherapy strategies in oncology and advancements in our understanding of molecular pathways that underpin cancer development have reignited interest in the tumor-associated antigen Folate Receptor alpha (FRα). FRα is a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Its overexpression in tumors such as ovarian, breast and lung cancers, low and restricted distribution in normal tissues, alongside emerging insights into tumor-promoting functions and association of expression with patient prognosis, together render FRα an attractive therapeutic target. In this review, we summarize the role of FRα in cancer development, we consider FRα as a potential diagnostic and prognostic tool, and we discuss different targeted treatment approaches with a specific focus on monoclonal antibodies. Renewed attention to FRα may point to novel individualized treatment approaches to improve the clinical management of patient groups that do not adequately benefit from current conventional therapies.

Modular Antigen‐Specific T‐cell Biofactories for Calibrated In Vivo Synthesis of Engineered Proteins

“…The rationale for the choice of these two antigens was based on the fact that they are overexpressed on multiple cancers and their expression on healthy tissues is rather limited. [9] In vivo activity and specificity of T-cell Biofactories were demonstrated in mice bearing sub-cutaneous OVCAR3 tumors (Figure 3). …”

Risk analysis of malignant potential of oral verrucous hyperplasia: A follow‐up study of 269 patients and copy number variation analysis

“…The FRs help transport folic acid and its reduced derivatives into cells, which promotes cancer malignancy through forming a signaling complex with transmembrane proteins to initiate intracellular regulatory signaling networks . The FR‐targeted approaches, such as antibodies, folate‐conjugates, and antifolates, were developed for cancer imaging and therapy in FRα‐overexpressing cancers, such as ovarian, uterine, breast, cervical, kidney, and colon carcinomas . Therefore, we speculated that FR‐targeted approaches may prevent oral verrucous hyperplasia transformation or could be therapeutics for oral verrucous hyperplasia‐related OSCC.…”

Development of oncolytic virotherapy: from genetic modification to combination therapy

“…The combination of OV expressing BiTE with CAR-T cells can also produce potent antitumor activity [228]. Folate receptor α (FR-α), highly expressed in ovarian, breast, and lung tumor cells, is an important target for antitumor therapy [229]. However, small partial tumor cells remain with low or even no expression of FR-α in those tumor lesions that can lead to immune escape.…”