Relationship between Changes of Serum Vascular Endothelial Growth Factor and Folate Receptor-α Levels and Clinical Efficacy of Toripalimab in Patients with Bladder Cancer.

OBJECTIVE: This study aims to explore the changes of serum vascular endothelial growth factor (VEGF) and folate receptor-α (FR-α) levels in patients with bladder cancer before and after treatment with toripalimab and to analyse the relationship between the changes of VEFG and FR-α and the clinical efficacy of patients. METHODS: A total of 176 patients with bladder cancer admitted to our hospital from January 2020 to January 2022 were selected as the research subjects. All patients were treated with toripalimab. The clinical efficacy and changes of serum VEGF and FR-α levels before and after treatment were observed. Logistic regression was used to analyse the relationship between serum VEGF and FR-α levels and the therapeutic effect of toripalimab, and receiver operating characteristic curve was used to evaluate the predictive value of serum VEGF and FR-α on the efficacy. RESULTS: The objective response rate and disease control rate after treatment were 31.82% and 70.45%, respectively. The serum VEGF and FR-α levels in patients after treatment were significantly lower than those before treatment (p < 0.001). The patients were divided into an effective group (n = 124) and an ineffective group (n = 52) according to clinical efficacy. The serum VEGF and FR-α levels of patients in the effective group were significantly lower than those of the ineffective group (p < 0.001). Logistic regression analysis showed that the elevated levels of serum VEGF (odds ratio = 1.226) and FR-α (odds ratio = 1.384) were the risk factors affecting the therapeutic effect of toripalimab (p < 0.05). The area under curve of the combined prediction of VEGF and FR-α was 0.920, the Youden index was 0.722, the sensitivity was 89.52%, the specificity was 82.69%, and the predictive value was higher than the single detection of VEGF or FR-α (p = 0.001, p < 0.001). CONCLUSIONS: The changes of serum VEGF and FR-α levels in patients with bladder cancer can predict the therapeutic effect of toripalimab. Before clinical treatment, the detection of the two indicators must be strengthened, and intervention measures must be formulated as early as possible to improve the prognosis of patients.

Relationship between Changes of Serum Vascular Endothelial Growth Factor and Folate Receptor-α Levels and Clinical Efficacy of Toripalimab in Patients with Bladder Cancer

Objective: This study aims to explore the changes of serum vascular endothelial growth factor (VEGF) and folate receptor-α (FR-α) levels in patients with bladder cancer before and after treatment with toripalimab and to analyse the relationship between the changes of VEFG and FR-α and the clinical efficacy of patients. Methods: A total of 176 patients with bladder cancer admitted to our hospital from January 2020 to January 2022 were selected as the research subjects. All patients were treated with toripalimab. The clinical efficacy and changes of serum VEGF and FR-α levels before and after treatment were observed. Logistic regression was used to analyse the relationship between serum VEGF and FR-α levels and the therapeutic effect of toripalimab, and receiver operating characteristic curve was used to evaluate the predictive value of serum VEGF and FR-α on the efficacy. Results: The objective response rate and disease control rate after treatment were 31.82% and 70.45%, respectively. The serum VEGF and FR-α levels in patients after treatment were significantly lower than those before treatment (p < 0.001). The patients were divided into an effective group (n = 124) and an ineffective group (n = 52) according to clinical efficacy. The serum VEGF and FR-α levels of patients in the effective group were significantly lower than those of the ineffective group (p < 0.001). Logistic regression analysis showed that the elevated levels of serum VEGF (odds ratio = 1.226) and FR-α (odds ratio = 1.384) were the risk factors affecting the therapeutic effect of toripalimab (p < 0.05). The area under curve of the combined prediction of VEGF and FR-α was 0.920, the Youden index was 0.722, the sensitivity was 89.52%, the specificity was 82.69%, and the predictive value was higher than the single detection of VEGF or FR-α (p = 0.001, p < 0.001)(AU)

Field-effect transistor bioassay for ultrasensitive detection of folate receptor 1 by ligand-protein interaction.

A miniaturized and integrated bioassay was developed based on molybdenum disulfide (MoS2) field-effect transistor (FET) functionalized with bovine serum albumin-folic acid (BSA-FA) for monitoring FOLR1. We performed the electrical test of FOLR1 within the range 100 fg/mL to 10 ng/mL, and the limit of detection was 0.057 pg/mL. The ultrahigh sensitivity of the bioassay was realized by ligand-protein interaction between FA and FOLR1, with a ligand-protein binding ratio of 3:1. The formation of FA-FOLR1 was confirmed with ELISA. The binding affinity dissociation constant KD was 12 ± 6 pg/mL. This device can work well for FOLR1 detection in human serum, which presents its promising application in point-of-care diagnosis. This study supports the future applications of such ligand-protein-based bioassays in the clinical practices. Graphical abstract MoS2-based FET device for detecting folate receptor 1 (FOLR1) was fabricated. The molecular folic acid as a probe can specifically bound to FOLR1 with a high affinity.

Characterization of soluble folate receptors (folate binding proteins) in humans. Biological roles and clinical potentials in infection and malignancy.

This review surveys soluble Folate Receptors (FOLRs) in humans. FOLR1 and FOLR2 are equipped with cellular glycosylphosphatidylinositol (GPI) anchors. FOLR1 is secreted from epithelia with or without a micelle-encapsulated GPI-anchor into milk and other body fluids/secretions, e.g. semen where its interaction with spermatozoa indicates a role in male fertility. FOLR1 and FOLR2 serve as serum biomarkers of various diseases. FOLR3 possesses no GPI-anchor and originates from secretory granules of neutrophil granulocytes; its concentration in serum correlates to the FOLR3 content in leukocytes and rises with increased leukocyte counts (infection, malignancy and pregnancy). FOLR3 exerts anti-microbial and anti-tumor effects by depriving bacteria and tumor cells of natural folates. Megalin receptors mediate reabsorption of ultrafiltered folate-bound FOLR into cells of proximal kidney tubules and of folate-bound FOLR uptake in growing embryos. Megalin receptors overexpressed in malignant tumors could be suitable therapeutic targets for folate-conjugated cytotoxic agents utilizing soluble FOLRs as vectors.

Folate-receptor 1 level in periodontal disease: a pilot study.

BACKGROUND: The purpose of this study was to investigate gingival crevicular fluid (GCF) and serum folate-receptor 1 (FOLR1) levels in subjects with different periodontal status. METHODS: The study consists of three groups: Healthy group (n = 15), gingivitis group (n = 15) and chronic periodontitis group (n = 15). Clinical periodontal parameters including probing pocket depth (PPD), clinical attachment level (CAL), gingival index (GI) and bleeding on probing (BOP) were assessed. GCF and serum samples were collected from each patient and were analyzed FOLR1 levels by enzyme-linked immunosorbent assay. RESULTS: The values of FOLR1 in GCF were higher in gingivitis and periodontitis groups than among patient in control group (p < 0.016). Serum FOLR1 levels showed no significant difference between the groups. A significant correlation was observed between FOLR1 levels of GCF and BOP (p < 0.05). CONCLUSIONS: Our preliminary data suggest that FOLR1 is not useful in monitoring the periodontal disease. Further studies are necessary to clarify the role, regulation and function of folate and it's receptors in the pathogenesis of periodontal disease.

Mild steel welding is associated with alterations in circulating levels of cancer-related proteins.

Welding fumes were recently classified as carcinogenic to humans and worldwide millions work as welders or perform welding operations. The purpose of this study was to identify new biomarkers of welding-induced carcinogenesis. We evaluated a panel of 91 putative cancer-related proteins in serum in a cohort of welders working with mild steel (n = 77) and controls (n = 94) from southern Sweden sampled on two occasions 6-year apart using a longitudinal analysis (linear mixed models). The significant results from the longitudinal analysis were tested for reproducibility in welders (n = 88) and controls (n = 69) sampled once during the same sampling period as timepoint 1 or timepoint 2 (linear regression models), i.e., in a cross-sectional setting. The models were adjusted for age, body-mass index, and use of snus. All study participants were non-smokers at recruitment. Exposure to welding fumes was assessed using questionnaires and respirable dust measurement in the breathing zone that was adjusted for personal respiratory protection equipment. The median respirable dust in welders was 0.7 (0.2-4.2) and 0.5 (0.1-1.9) mg/m3 at the first and second timepoints, respectively. We identified 14 cancer-related proteins that were differentially expressed in welders versus controls in the longitudinal analysis, out of which three were also differentially expressed in the cross-sectional analysis (cross-sectional group). Namely, syndecan 1 (SDC1), folate receptor 1 (FOLR1), and secreted protein acidic and cysteine rich (SPARC) were downregulated, in welders compared with controls. In addition, FOLR1 was negatively associated with years welding. Disease and function analysis indicated that the top proteins are related to lung cancer as well as cell invasion and migration. Our study indicates that moderate exposure to welding fumes is associated with changes in circulating levels of putative cancer-related proteins, out of which FOLR1 showed a clear dose-response relationship. It is, however, unclear to which extent these changes are adaptive or potential early biomarkers of cancer.

Serum folate receptor α (sFR) in ovarian cancer diagnosis and surveillance.

Novelty and Impact Statement: Our findings suggest that soluble folate receptor (sFR) could be used in both the initial diagnosis and surveillance of patients with ovarian cancer. Our cohort constitutes one of the largest comparison groups for sFR analyzed so far. We have defined the background level of sFR using healthy volunteers. This is also the first study to prospectively follow patients in the surveillance setting to concurrently identify differential changes in tumor markers CA-125 and sFR.

Validation of a Novel Biomarker Panel for the Detection of Ovarian Cancer.

BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy. Our integrated -omics approach to ovarian cancer biomarker discovery has identified kallikrein 6 (KLK6) and folate-receptor 1 (FOLR1) as promising candidates but these markers require further validation. METHODS: KLK6, FOLR1, CA125, and HE4 were investigated in three independent serum cohorts with a total of 20 healthy controls, 150 benign controls, and 216 ovarian cancer patients. The serum biomarker levels were determined by ELISA or automated immunoassay. RESULTS: All biomarkers demonstrated elevations in the sera of ovarian cancer patients compared with controls (P < 0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify ovarian cancer patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. In addition, the combination of HE4 and FOLR1 was a strong predictor of ovarian cancer diagnosis, displaying comparable sensitivity (65%) to the best-performing CA125-based models (67%) at a set specificity of 95%. CONCLUSIONS: The markers identified through our integrated -omics approach performed similarly to the clinically approved markers CA125 and HE4. Furthermore, HE4 represents a powerful diagnostic marker for ovarian cancer and should be used more routinely in a clinical setting. IMPACT: The implications of our study are 2-fold: (i) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (ii) we have demonstrated the clinical utility of our integrated -omics approach to identifying novel serum markers with comparable performance to clinical markers. Cancer Epidemiol Biomarkers Prev; 25(9); 1333-40. ©2016 AACR.

Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy.

The role of folate receptor autoantibodies in preterm birth.

OBJECTIVE: Cellular uptake of folate is mediated by folate receptor (FR)α. Prior studies indicate that a FRα autoantibody (FRAb) is implicated in poor pregnancy outcomes. The aims of this study were to determine the prevalence of FRAbs in women with preterm and term pregnancies, and to investigate the role of maternal FRAbs in preterm birth. METHODS: This prospective observational study included 23 mothers and 25 preterm infants (two twin births) born at gestational age (GA) ≤32 wk and/or birth weight ≤1500 g (group 1) and 25 mother-term infant pairs (infants born at GA ≥37 wk, group 2). Blocking and binding FRAbs in maternal and in cord blood were determined. The association between maternal FRAbs and pregnancy outcome was measured using multiple logistic regression, adjusted for maternal age and previous preterm birth. RESULTS: The prevalence of FRAbs was 65.2% in women with preterm birth, which was twofold higher than in those with term pregnancy (28%; relative risk [RR], 2.3; 95% confidence interval [CI], 1.2-4.7). The prevalence of FRAbs in preterm infants (64%) was significantly higher than in term infants (24%; RR, 2.7; 95% CI, 1.3-5.7). Pregnant women with positive FRAbs had 4.9 times higher odds of having preterm birth (odds ratio, 4.9; 95% CI, 1.4-17.7), adjusted for maternal age and previous preterm birth. CONCLUSIONS: These findings suggest that the presence of FRAbs might be a contributing factor to preterm birth, which could be prevented with appropriate testing and therapeutic interventions. Further studies are warranted to investigate the possible mechanisms of fetal sensitization resulting in FRAb production in utero and its possible clinical correlates.

Conditions associated with circulating tumor-associated folate receptor 1 protein in healthy men and women.

BACKGROUND: Serum concentrations of the tumor-associated folate receptor 1 (FOLR1) protein may be a marker for early cancer detection, yet concentrations have also been detected in cancer-free women. We investigated the conditions associated with circulating FOLR1 protein in healthy individuals and sought to clarify the range of normal serum values. METHODS: Sera of cancer-free men and women (N = 60) enrolled in a population-based cohort study in Alberta, Canada were analyzed for FOLR1 protein using an electrochemical luminescence immunoassay. Dietary, lifestyle, medical and reproductive history information was collected by questionnaires. Differences in serum FOLR1 concentrations between groups were assessed by non-parametric tests, and predictors of serum FOLR1 concentrations were estimated using multivariable linear regression. RESULTS: Median serum FOLR1 concentration was higher in women (491 pg/ml, range = 327-693 pg/ml) than in men (404 pg/ml, range = 340-682 pg/ml), P = 0.001. FOLR1 concentration was also positively associated with vitamin A intake (P = 0.02), and showed positive trends with age and with oral contraceptive hormone use among women and an inverse trend with body mass index. All variables examined explained almost half of the variation in serum FOLR1 (model R2 = 0.44, P = 0.04); however, the retention of gender (P = 0.003) and vitamin A intake (P = 0.03) together explained 20% (P = 0.001) of serum FOLR1 variation. No other predictor was significant at P<0.05. CONCLUSIONS: The positive association between serum FOLR1 concentration and female gender independent of an age effect suggests caution against statements to exploit serum FOLR1 for early cancer detection without further understanding the biological underpinnings of these observations. Serum FOLR1 concentrations may be influenced by the steroid retinoic acid (vitamin A) but do not appear to be associated with folate nutritional status. These findings require confirmation in larger independent studies.

Quantitation of rare circulating tumor cells by folate receptor α ligand-targeted PCR in bladder transitional cell carcinoma and its potential diagnostic significance.

Numerous attempts for detection of circulating tumor cells (CTC) have been made to develop reliable assays for early diagnosis of cancers. In this study, we validated the application of folate receptor α (FRα) as the tumor marker to detect CTC through tumor-specific ligand PCR (LT-PCR) and assessed its utility for diagnosis of bladder transitional cell carcinoma (TCC). Immunohistochemistry for FRα was performed on ten bladder TCC tissues. Enzyme-linked immunosorbent assay (ELISA) for FRα was performed on both urine and serum specimens from bladder TCC patients (n = 64 and n = 20, respectively) and healthy volunteers (n = 20 and n = 23, respectively). Western blot analysis and qRT-PCR were performed to confirm the expression of FRα in bladder TCC cells. CTC values in 3-mL peripheral blood were measured in 57 bladder TCC patients, 48 healthy volunteers, and 15 subjects with benign urologic pathologies by the folate receptor α ligand-targeted PCR. We found that FRα protein was overexpressed in both bladder TCC cells and tissues. The levels of FRα mRNA were also much higher in bladder cancer cell lines 5637 and SW780 than those of leukocyte. Values of FRα were higher in both serum and urine specimens of bladder TCC patients than those of control. CTC values were also higher in 3-mL peripheral blood of bladder TCC patients than those of control (median 26.5 Cu/3 mL vs 14.0 Cu/3 mL). Area under the receiver operating characteristic (ROC) curve for bladder TCC detection was 0.819, 95 % CI (0.738-0.883). At the cutoff value of 15.43 Cu/3 mL, the sensitivity and the specificity for detecting bladder cancer are 82.14 and 61.9 %, respectively. We concluded that quantitation of CTCs through FRα ligand-PCR could be a promising method for noninvasive diagnosis of bladder TCC.

Association of folic acid receptor α in maternal serum with neural tube defects.

OBJECTIVE: To evaluate whether serum folic receptor α levels are changed in women whose previous pregnancies were complicated with neural tube defects (NTDs). METHODS: This was a case-control study that included 41 women as the control group who had previously had at least one healthy pregnancy and 37 women as the study group who had a previous pregnancy complicated with NTDs. Blood samples were obtained from all of the participants six weeks after the termination of pregnancy or delivery of a baby. Serum folate receptor α concentrations were analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The mean concentrations of serum folate receptor α were significantly lower in the NTD cases compared to those in the control group (p = 0.02). There was no significant difference in mean serum folate titers between the NTD cases and the control group (p = 0.07). CONCLUSION: Low serum folic acid receptor α levels in the current study did not appear to be a regulatory marker of maternal folate homeostasis per se but rather a factor that contributed to the development of NTDs.

Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients.

OBJECTIVES: Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women. DESIGN AND METHODS: FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate. RESULTS: FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (P<0.0001) and patients with benign gynecological conditions (P<0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125. CONCLUSIONS: FOLR1 is a new biomarker for ovarian cancer which correlates closely with CA125. The role of FOLR1 in the pathogenesis of ovarian cancer warrants further investigation.

A folate receptor electrochemical sensor based on terminal protection and supersandwich DNAzyme amplification.

Based on the protecting effect of folate receptor (FR) toward folic acid (FA) modified DNA and the signal amplification of supersandwich DNA structure, we designed an interesting electrochemical biosensor for FR. In the present system, with the increase of FR, protecting more FA bound DNA from hydrolysis by exonuclease I (Exo I), FA bound DNA will hybridize to form more supersandwich DNA structure resulting in an increased electrochemical signal. A relationship between the concentration of the target protein, FR, and the obtained electrochemical signal can be established. The signal was obtained by the catalysis on H2O2 in the system containing Fc and hemin/DNAzyme. The detection concentration range of FR was from 1.0 to 20.0 ng/mL with an achieved detection limit of 0.3 ng/mL which approached clinically relevant concentrations of FR.

Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.

BACKGROUND: Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor α (FRα), as well as possible effects of parental demographics or prenatal exposures. METHODS: We conducted a nested case-control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n = 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n = 221). The inhibition of folic acid binding to FRα was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors. RESULTS: There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0-1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FRα (CL/P aOR = 0.7, 95% CI 0.6-1.0; CPO aOR = 1.1, 95% CI 0.8-1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FRα. CONCLUSIONS: Inhibition of folic acid binding to FRα in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.

Harnessing engineered antibodies of the IgE class to combat malignancy: initial assessment of FcɛRI-mediated basophil activation by a tumour-specific IgE antibody to evaluate the risk of type I hypersensitivity.

BACKGROUND: IgE antibodies, sequestered into tissues and retained locally by the high-affinity IgE receptor, FcɛRI, on powerful effector cells such as mast cells, macrophages and eosinophils, may offer improvements in the therapy of solid tumours. The chimeric antibody, MOv18 IgE, against the human ovarian carcinoma antigen, folate receptor α (FRα), is more effective than its IgG1 counterpart in xenograft models of ovarian cancer. Although MOv18 IgE binds to a single epitope on FRα and cannot cross-link IgE receptors on basophils, there remains a risk that components in the circulation of ovarian cancer patients might cross-link FRα-MOv18-IgE-receptor-FcɛRI complexes on basophils to cause type I hypersensitivity. OBJECTIVE: To assess the propensity for MOv18 used in a therapeutic setting to cause FcɛRI-mediated type I hypersensitivity. METHODS: As validated readouts of the potential for MOv18 to cause FcɛRI-mediated type I hypersensitivity we measured release of a granule-stored mediator from a rat basophilic leukaemia cell line RBL SX-38 stably transfected with human tetrameric (αßγ2) FcɛRI, and induction of CD63 on blood basophils from patients with ovarian carcinoma and healthy controls ex vivo. RESULTS: Serum FRα levels were increased in ovarian cancer patients compared with healthy controls. MOv18 IgE alone, or in the presence of its antigen recombinant human FRα, or of healthy volunteer (n=14) or ovarian carcinoma patient (n=32) sera, did not induce RBL SX-38 cell degranulation. Exposure to FRα-expressing ovarian tumour cells at target-to-effector ratios expected within tumours induced degranulation. MOv18 IgE did not induce expression of CD63 in blood basophils from either healthy volunteers (n=6), or cancer patients, despite detectable levels of circulating FRα (n=5). CONCLUSION AND CLINICAL RELEVANCE: These encouraging data are compatible with the hypothesis that, when ovarian carcinoma patients are treated with MOv18, FcɛRI-mediated activation of effector cells occurs within the tumour mass but not in the circulation mandating, with due caution, further pre-clinical studies.