Overexpression of folate binding protein in ovarian cancers

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

“…5,6 Intrabodies are potentially suited for antiviral and antitumor gene therapy approaches, and preclinical and clinical studies have been promising. 7,8 One of the more specific tumor markers identified in our laboratory 9 is the a-isoform of the folate receptor (FR), a 38-40 kDa glycosyl-phosphatidyl-inositol-anchored molecule [10][11][12][13] that binds folic acid with high affinity. Detailed immunohistochemical analysis and evaluation of messenger RNA expression revealed moderate levels of FR expression on the cell surface of normal epithelial cells of kidney, lung and breast, and high levels in placental tissue.…”

“…Detailed immunohistochemical analysis and evaluation of messenger RNA expression revealed moderate levels of FR expression on the cell surface of normal epithelial cells of kidney, lung and breast, and high levels in placental tissue. 9,14-17 FR is not expressed in normal ovarian surface epithelium (OSE) 18 but is selectively overexpressed in the vast majority of nonmucinous ovarian carcinomas, 9,13 which arise from OSE. The association of FR expression with progression of the disease 13 has implicated this molecule in malignant transformation of this tissue.…”

“…9,14-17 FR is not expressed in normal ovarian surface epithelium (OSE) 18 but is selectively overexpressed in the vast majority of nonmucinous ovarian carcinomas, 9,13 which arise from OSE. The association of FR expression with progression of the disease 13 has implicated this molecule in malignant transformation of this tissue. We recently showed that FR affects cell proliferation of ovarian carcinoma cells not only by mediating folate uptake but also by generating intracellular signals that are associated with dysregulated cell proliferation.…”

DNA vaccination against the ovarian carcinoma-associated antigen folate receptor α (FRα) induces cytotoxic T lymphocyte and antibody responses in mice

“…In fact, the FR␣ overexpression in human ovarian carcinomas seems to be an early event during the transformation process, and is maintained or even increased during tumor progression, suggesting that this molecule is essential for tumor cell life. 25 Moreover, no Ag loss variants could be detected in patients whose disease relapsed after passive immunotherapy with anti-FR␣ mAb 26 or after adoptive transfer of lymphocytes retargeted with anti-FR␣/anti-CD3 bispecific mAb. 27 In conclusion, our data indicate that human FR␣ DNA vaccination is effective in mice and may deserve further investigations to evaluate its possible application for immunotherapy of human ovarian cancer.…”

“…17 The ␣ isoform of the folate receptor (FR), a 38-to 40-kDa glycosylphosphatidylinositol-anchored molecule, 18 -20 is expressed at very low levels on the cell surface of normal epithelial tissues; at medium levels on the kidney, lung, and breast; and at high levels on placental tissue. [21][22][23] Overexpression of FR␣ has been detected on ϳ90% of ovarian carcinomas 23,24 in association with the progression of the disease, 25 on epithelial tumors derived from the uterus, and on nervous system tumors. 22 Based on its expression pattern, FR␣ has been used as a target molecule for monoclonal Ab (mAb)-based immunotherapy strategies.…”