Folate-Hapten-Mediated Immunotherapy Synergizes with Vascular Endothelial Growth Factor Receptor Inhibitors in Treating Murine Models of Cancer.

The overexpression of folate receptors (FR) on many human cancers has led to the development of folate-linked drugs for the imaging and therapy of FR-expressing cancers. In a recent phase I clinical trial of late-stage renal cell carcinoma patients, folate was exploited to deliver an immunogenic hapten, fluorescein, to FR tumor cells in an effort to render the cancer cells more immunogenic. Although >50% of the patients showed prolonged stable disease, all patients eventually progressed, suggesting that the folate-hapten immunotherapy was insufficient by itself to treat the cancer.