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At least 19 recordsLinked to original sources
PubMed2005

Serum antibodies to EpCAM in healthy donors but not ulcerative colitis patients.

PURPOSE: The gastrointestinal carcinoma-associated antigen epithelial cell adhesion molecule (EpCAM) has been a target for passive and active immunotherapy of gastrointestinal carcinoma patients. The antigen is expressed by both tumor and normal tissues. The immunogenicity of EpCAM in colorectal cancer patients has been described previously. The purpose of this study was to evaluate humoral and cellular immune responses of healthy individuals and ulcerative colitis patients to EpCAM and to relate immune responses to colonic tissue expression of EpCAM. METHODS: An inhibition radioimmunoassay was used to detect anti-EpCAM serum antibodies. Anti-EpCAM antibodies of a healthy donor were expressed by phages and sequenced. (3)H-thymidine incorporation assay was used for detection of lymphoproliferative responses to stimulation with EpCAM. EpCAM tissue expression was determined by immunohistochemistry. RESULTS: We detected anti-EpCAM serum antibodies in 4 of 10, and EpCAM-specific lymphoproliferation responses in 1 of 10 healthy volunteers. The majority of anti-EpCAM antibodies derived from a healthy donor were germline-encoded. In contrast, none of the 23 patients with ulcerative colitis showed serum antibodies to EpCAM (P=0.005). Antigen expression was greatly reduced and altered in ulcerative colitis patients, whereas colon from healthy individuals and uninvolved colon of colorectal cancer patients expressed high levels of EpCAM. CONCLUSION: The results of these studies suggest an association between EpCAM antibody production and colonic EpCAM expression in healthy individuals and patients with ulcerative colitis. Decreased and altered colonic EpCAM expression in ulcerative colitis patients may be related to the disease induction, based on the previously demonstrated adhesion function of this molecule. Healthy individuals with anti-EpCAM immune responses and high risk for developing colorectal carcinoma are prime candidates for prophylactic immunization against EpCAM.

Adult↗
PubMed2007

Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of the tongue and its possibility as a potential target for tongue cancer gene therapy.

Epithelial adhesion molecule (EpCAM) is a transmembrane glycoprotein involved in intercellular adhesion. In particular, EpCAM appears to be overexpressed by the majority of human epithelial carcinomas, including colorectal, breast, head and neck, and hepatic carcinomas. We therefore hypothesized that EpCAM would be a good molecular target for cancer gene therapy. EpCAM protein expression in 48 primary tongue cancers and 10 normal oral mucosa was evaluated using anti-EpCAM immunohistochemistry, and correlation was examined with the clinicopathologic factors. In four human tongue cancer cell lines (SAS, HSC-2, OSC19 and OSC20), we investigated EpCAM expression by reverse transcription-polymerase chain reaction (RT-PCR). The invasive potential of cancer cells was evaluated using Matrigel invasion assay. Moreover, the effect of EpCAM inhibition was analyzed using RNA interference (RNAi). EpCAM overexpression was detected in 30 of 48 tongue cancers (62.5%), and was significantly higher in primary squamous cell carcinoma (SCC) of the tongue than in normal oral mucosa. The expression of EpCAM was significantly associated with tumor size, regional lymph node metastasis, histological differentiation and invasion pattern. Cancer cell lines with higher EpCAM expression had more invasive potential. Moreover, RNAi-mediated EpCAM reduction decreased the invasion potential and proliferation activity. These results indicated that the overexpression of EpCAM was correlated with a more aggressive phenotype of tongue cancer. Moreover, we suggested that EpCAM could be a molecular target, and that RNAi targeting EpCAM could be useful for tongue cancer gene therapy.

Aged↗
PubMed2004

[Construction and expression of human EpCAM eukaryotic expression vectors and identification of their products].

AIM: To construct EpCAM eukaryotic expression vectors pIg-EpCAM and pEGFP-EpCAM and to express them in COS7 cells. METHODS: EpCAM cDNA was amplified by PCR and then inserted into the pIg and pEGFP vectors respectively to construct recombinant vectors pIg-EpCAM and pEGFP-EpCAM. The two recombinant vectors were transfected into COS7 cells under the mediation of liposome. The expressed EpCAM-Ig fusion protein was detected by Western blot. The expression of EpCAM-GFP fusion protein was observed under fluorescence microscope. RESULTS: DNA sequencing demonstrated that EpCAM was correctly cloned into the two vectors. The culture supernatant of the pIg-EpCAM-transfected COS7 cells could bind effectively to mAb against human IgG Fc. Green fluorescence distributed evenly in the cytoplasm and nuclei of pEGFP-transfected COS7 cells, whereas in pEGFP-EpCAM transfected COS7 cells, green fluorescence distributed mainly on the surface of the cells. CONCLUSION: Two EpCAM eukaryotic expression vectors have been constructed and expressed successfully, which lays the foundation for functional research of EpCAM and for preparation of mAb to EpCAM.

Animals↗
PubMed2004

EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy.

EpCAM (epithelial cell adhesion molecule) is a cell surface molecule that is known to be highly expressed in colon and other epithelial carcinomas. EpCAM is involved in cell-to-cell adhesion and has been the target of antibody therapy in several clinical trials. To assess the value of EpCAM as a novel target for breast cancer gene therapy, we performed real-time reverse transcription-PCR to quantify the level of EpCAM mRNA expression in normal breast tissue and primary and metastatic breast cancers. We found that EpCAM is overexpressed 100- to 1000-fold in primary and metastatic breast cancer. Silencing EpCAM gene expression with EpCAM short interfering RNA (siRNA) resulted in a 35-80% decrease in the rate of cell proliferation in four different breast cancer cell lines. EpCAM siRNA treatment decreased cell migration by 91.8% and cell invasion by 96.4% in the breast cancer cell line MDA-MB-231 in vitro. EpCAM siRNA treatment was also associated with an increase in the detergent-insoluble protein fraction of E-cadherin, alpha-catenin, and beta-catenin, consistent with the known biology of EpCAM as a regulator of cell adhesion. Our hypothesis is that modulation of EpCAM expression can affect cell migration, invasion, and proliferation by enhancing E-cadherin-mediated cell-to-cell adhesion. These data provide compelling evidence that EpCAM is a potential novel target for breast cancer gene therapy and offer insights into the mechanisms associated with EpCAM gene silencing.

Antigens, Neoplasm↗
PubMed2005

Clinical effects of a chimeric anti-EpCAM monoclonal antibody in combination with granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal carcinoma.

The EpCAM antigen is highly expressed on colorectal carcinoma (CRC) cells. Murine anti-EpCAM MAb (anti-EpCAM mMAb) alone or in combination with cytokines may induce clinical responses including long-lasting complete remissions (CR) in patients with metastatic disease. The chimeric variant of anti-EpCAM MAb (anti-EpCAM cMAb) interacts more efficiently with human effector cells (ADCC) than the murine counterpart in the killing of colorectal carcinoma cells in vitro, an important mechanism of action for antibody in vivo. Granulocyte-macrophage colony-stimulating factor (GM-CSF) augments immune effector cell functions in vivo and may enhance the therapeutic effect of MAbs. In this study, the therapeutic efficacy of the combination of anti-EpCAM cMAb and GM-CSF was evaluated in 24 patients with metastatic CRC. GM-CSF was given s.c. once daily for 10 consecutive days and on day 3, anti-EpCAM cMAb was given i.v. A treatment cycle was repeated every 4th week. Five patients achieved stable disease > 3 months (overall response rate 21%). Responding patients survived significantly longer than non-responding patients (p = 0.030). The frequency of patients with an immediate-type allergic reaction (ITAR) against anti-EpCAM cMAb at the 1st, 2nd, 3rd and 4th treatment cycles was as 13%, 29%, 25% and 19% respectively. Compared to a previous study where anti-EpCAM mMAb was used in a similar treatment regimen, the present protocol did not augment the overall or progression-free survival. The overall response rate was also similar to anti-EpCAM mMAb treated patients (6/22, 27%), but the anti-EpCAM mMAb treatment protocol induced two CR, one MR and three SD. Further studies are warranted to establish the role of EpCAM as a target for antibody therapy, specifically the significance of chimeric or humanized anti-EpCAM MAbs.

Aged↗
PubMed2007

Prognostic significance of EpCAM expression in human esophageal cancer.

EpCAM is a 40-kDa epithelial transmembrane glycoprotein that has a well-known role in Ca2+ -independent homophilic cell-cell adhesion. Recently, correlations between EpCAM expression and clinicopathological features have been investigated in various cancers. We examined EpCAM expression in surgical specimens from esophageal cancer patients (n = 138), using real-time RT-PCR, immunohistochemistry and ELISA. The mean expression level of EpCAM mRNA in tumor tissues was significantly higher than that in corresponding normal tissues (P < 0.0001). Immunohistochemically, positive staining for EpCAM was found in 135 (97.8%) of the 138 primary tumor specimens. EpCAM expression was correlated with tumor depth (P = 0.0005), stage (P = 0.0037), blood-vessel invasion (P = 0.0397) and infiltrative growth pattern (P = 0.0015). The survival rates of patients with tumors with high EpCAM expression was significantly higher than those for patients with tumors with low EpCAM expression (P = 0.0213). Furthermore, the serum EpCAM levels of patients with esophageal cancer were significantly higher than those of normal volunteers (P = 0.0221). The survival rates of patients with a high EpCAM level in the peripheral vein were also significantly higher than those for patients with a low serum EpCAM level (P = 0.0291). The serum EpCAM level in the peripheral vein was independently associated with prognosis (P = 0.0074; hazard ratio 7.40). Tumor-specific EpCAM expression and release into the circulation may serve as effective immunotherapy in esophageal cancer patients.

Aged↗
PubMed2004

The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation.

Epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein expressed on adenomatous and simple epithelia, where it is involved in homophilic adhesion at the basolateral membrane. Carcinomas strongly overexpress EpCAM through an, as yet, unknown mechanism. Interestingly, otherwise EpCAM-negative squamous epithelia are seen to express EpCAM concomitant with their transformation and de-differentiation. The amount of EpCAM and the number of expressing cells both increase with the grade of dysplasia. Despite an important amount of data correlating the expression of EpCAM with cellular proliferation and de-differentiation, such as the coexpression with Ki-67, a marker for proliferation, it is unknown whether EpCAM may directly contribute to carcinogenesis. Here, we show that EpCAM has a direct impact on cell cycle and proliferation, and the ability to rapidly upregulate the proto-oncogene c-myc and cyclin A/E. Human epithelial 293 cells as well as murine NIH3T3 fibroblasts expressing EpCAM had a decreased requirement for growth factors, enhanced metabolic activity and colony formation capacity. Importantly, the inhibition of EpCAM expression with antisense mRNA led to a strong decrease in proliferation and metabolism in human carcinoma cells. Moreover, domain swapping experiments demonstrated that the intracellular part of EpCAM is necessary and sufficient to transduce the effects described. Thus, the data presented here highlight the role of EpCAM, demonstrating for the first time a direct link to cell cycle and proliferation.

3T3 Cells↗
PubMed1999

Tumor-specific gene transfer via an adenoviral vector targeted to the pan-carcinoma antigen EpCAM.

The utility of adenoviral vectors for cancer therapy is limited due to their lack of specificity for tumor cells. In order to target adenovirus to tumor, the natural tropism of the adenovirus should be ablated and replaced by a tumor-specific binding domain. To this end, a neutralizing anti-fiber antibody conjugated to an anti-EpCAM antibody was created that targets the adenovirus to the EpCAM antigen present on tumor cells. The EpCAM antigen was chosen as the target because this antigen is highly expressed on a variety of adenocarcinomas of different origin such as breast, ovary, colon and lung, whereas EpCAM expression is limited in normal tissues. In these studies, the EpCAM-targeted adenovirus was shown to infect specifically cancer cell lines of different origin expressing EpCAM such as ovary, colon and head and neck. Gene transfer was blocked by excess anti-EpCAM antibody and dramatically reduced in EpCAM negative cell lines, thus showing the specificity of the EpCAM-targeted adenovirus. Importantly, infection with targeted adenovirus was independent of CAR, which is the natural receptor for adenovirus binding, since blocking of CAR with recombinant fiber knob did not affect infection with targeted adenovirus. Apart from the cancer cell lines, the efficacy of targeted viral infection was studied in freshly isolated primary human colon cancer cells. As colon cancer predominantly metastasizes to liver, and adenovirus has a high tropism for hepatocytes, we also sought to determine if the EpCAM-targeted adenovirus showed reduced infectivity of human liver cells. The bispecific antibody could successfully mediate gene transfer to primary human colon cancer cells, whereas it almost completely abolished infection of liver cells. This work thus demonstrates that EpCAM-targeted adenoviral vectors can be specifically directed to a wide variety of adenocarcinomas. This approach may prove to be useful for selective gene therapy of cancer.

Adenocarcinoma↗
PubMedDate not supplied

Limited suitability of EpCAM for molecular staging of tumor borders in head and neck cancer.

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is expressed in most normal epithelia, but is absent from squamous stratified epithelia. However, a de novo expression can be observed in squamous epithelia during carcinogenesis. MATERIALS AND METHODS: In order to evaluate EpCAM as a molecular marker to indicate borders of high risk for the development of local recurrences, its expression was examined in the marginal zone of malignancies. Specimens of squamous cell carcinoma of the head and neck (SCCHN), of the histologically tumor-free defined resection margin and of healthy epithelia of 20 patients were examined by RT-PCR in order to identify the expression of EpCAM in these three different areas. Additionally, immunohistochemistry was perfonned on biopsies from 10 patients in order to confirm these findings and to investigate a potential correlation between EpCAM expression and the degree of dysplasia. RESULTS: By RT-PCR, high expression of EpCAM was found in the tumor. An inverse correlation was observed between EpCAM expression and the distance from the tumor, with no expression being detectable in healthy oral mucosa. In 70% of the cases, EpCAM was expressed in the marginal zone, which had been defined as tumor-free by routine histopathological assessment. Additional immunohistology revealed no correlation between EpCAM expression and the grade of dysplasia. CONCLUSION: Our data provide evidence that EpCAM is restricted as a marker for redefining the real tumor margin by RT-PCR. To complement routine histology, immunohistochemical staining with EpCAM is limited due to its expression in hyperplastic tissue without dysplastic changes. Both observations limit the reliable use of EpCAM for the molecular definition of the critical tumor border and resection margins.

Aged↗
PubMed2006

Peptide arrays for the determination of humoral responses induced by active immunization with a monoclonal antibody against EpCAM.

Epithelial cell adhesion molecule (EpCAM) is an attractive target for monoclonal antibody serotherapy because it is over-expressed in approximately 70% of epithelial cancers and their metastatic lesions. IGN101, the immunogenic formulation of the murine monoclonal anti-EpCAM antibody Mab17-1A, has been shown to evoke a strong humoral immune response in both monkey studies and early clinical trials. Notably, there was a reduction in the number of circulating EpCAM-positive tumor cells in the peripheral blood of treated cancer patients. In contrast to earlier publications by other groups, we could not detect an anti-EpCAM immune response upon treatment with Mab17-1A using a conventional but optimized anti-EpCAM ELISA. Therefore, in a novel experimental setup, sera of healthy immunized monkeys, normal human donors and cancer patients immunized with IGN101 were tested for reactivity against a series of overlapping synthetic peptides encompassing the entire sequence of EpCAM prepared by SPOT synthesis on cellular supports. Using this method, sera from normal donors reacted with different peptides compared to sera from healthy monkeys. However, the peptides were clustered in the same regions of EpCAM. Cancer patients generally had a lower reactivity to EpCAM peptides and immunization with IGN101 induced reactivity against a different set of peptides. Antibodies cross-reacting with both the IgG2a framework and with the Mab17-1A idiotype were identified. In summary, our data indicate that some EpCAM peptides may be recognized in a species-specific manner. At least seven EpCAM-derived peptides could be of diagnostic interest (QCQCTSVGAQ, ERVRTYWIII, ALQKEITTRY, TYWIIIELKH, IADVAYYFEK, AYYFEKDVKG, GQTLIYYVDE), while four out of these seven peptides may also possess therapeutic relevance (TYWIIIELKH, ALQKEITTRY, IADVAYYFEK, AYYFEKDVKG).

Amino Acid Sequence↗
PubMed2005

Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors.

EpCam is an epithelial adhesion molecule expressed in a broad range of carcinomas. Clinical trials with specific humanized anti-EpCam antibodies have shown promising results and have been inaugurated in renal cell carcinoma (RCC) therapy. To study the EpCam expression profile, primary renal cell neoplasms as well as corresponding metastases were evaluated by immunohistochemistry in tissue microarrays. EpCam expression in oncocytomas and chromophobe RCCs was determined on conventional large sections. Moderate or strong EpCam expression was found in eighteen percent of clear cell (n=147), 75% of chromophobe (n=12), and 55% of papillary RCCs (n=20), but not in oncocytomas (n=3). On large sections, 90% of chromophobe RCCs (n=20) showed a strong and homogeneous positivity, whereas oncocytomas (n=15) revealed EpCam positivity in single tumor cells or small clusters. Fourteen percent of RCC metastases (n=97) showed EpCam expression. Patients with EpCam expressing clear cell RCC showed a trend toward a better prognosis in a Cox regression analysis including stage, grade, and necrosis. The data suggest EpCam as a potential therapeutic target in a subset of patients with RCC. In addition, expression patterns of EpCam could become a helpful tool in the discrimination of chromophobe RCC and oncocytoma.

Adult↗
PubMed2004

EpCAM expression in retinoblastoma: a novel molecular target for therapy.

PURPOSE: This study was conducted to investigate the potential of targeting epithelial cell adhesion molecules (EpCAMs) in the treatment of retinoblastoma. It was first determined whether EpCAM is expressed in retinoblastoma and then whether EpCAM reactivity correlates with tumor aggressiveness. METHODS: EpCAM reactivity was evaluated by immunohistochemistry in 43 retinoblastoma specimens from 43 patients, by using the monoclonal antibody GA733.2. The tumors were divided into two groups. There were 20 tumors with no invasion of the choroid and optic nerve (group A) and 23 tumors with invasion of the choroid, optic nerve, and orbit (group B). EpCAM reactivity was correlated with invasion and differentiation of the tumors. RESULTS: Among the 43 tumors, EpCAM reactivity was observed in 100% (43/43) tumors. EpCAM reactivity was significantly higher in the invasive than the noninvasive tumors (P < 0.05) and in poorly differentiated than in well-differentiated tumors (P < 0.005). Non-neoplastic retina also expressed EpCAM. CONCLUSIONS: The results confirm that EpCAM is vastly expressed in retinoblastoma and point to its use as a target for therapy in the future.

Adult↗
PubMedDate not supplied

Targeted gene expression using a 1.1 kilobase promoter fragment of the tumour-associated antigen EpCAM.

The epithelial cell adhesion molecule EpCAM is over- or de novo expressed during carcinogenesis. EpCAM expression correlates with increased proliferation and dedifferentiation. Recently, we reported the cloning of a 1.1 kilobase fragment upstream of the epcam gene and demonstrated its specific transcriptional activity. Here, we analyzed the potential of this fragment for targeted gene expression. The fragment was used to regulate the expression of the green fluorescent protein (GFP) and HSV-1 thymidine kinase (HSV-TK), as a model therapeutic gene. Transfection of the pEpProm-control or pEpProm-GFP plasmids resulted in the expression of functional GFP and HSV-TK proteins specifically in EpCAM-positive cells. Expression levels of both proteins correlated with the amount of EpCAM. Additionally, the targeted expression of HSV1-TK transferred a marked sensitivity to ganciclovir treatment in EpCAM-positive HEK293-EBNA1 and SkBr3 carcinoma cells. The EpCAM promoter fragment is, thus, a novel tool to allow for the transcription of therapeutic genes, specifically, in EpCAM-positive carcinomas.

Antigens, Neoplasm↗
PubMed2004

The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP.

The epithelial cell adhesion molecule, EpCAM, is a transmembrane glycoprotein associated with both benign and malignant proliferation. In cancer cells, expression levels of this tumour-associated antigen correlate positively with the grade of dysplasia and are also a negative prognostic factor for breast cancer patients. De novo expression of EpCAM resulted in the rapid upregulation of the proto-oncogene c-Myc along with enhanced cell proliferation and metabolism. Here, we analyzed the effects of EpCAM onto the proteome of epithelial cells. The epidermal fatty acid binding protein, E-FABP, was identified as a new EpCAM-regulated protein. E-FABP is a major target of c-Myc and was rapidly upregulated upon induction of EpCAM. Additionally, E-FABP levels correlated with the amount of EpCAM in permanent squamous cell carcinoma lines and in vivo in primary head and neck carcinomas. Taken together, these results provide further evidence for the direct involvement of EpCAM in signalling processes, gene regulation, and cellular metabolism supporting its important role in tumour biology.

Antigens, Differentiation↗
PubMed2004

Frequent EpCam protein expression in human carcinomas.

Expression of the transmembrane glycoprotein EpCam (epithelial cellular adhesion molecule) occurs in normal epithelium of different organs and was described in carcinomas of various sites. Specific anti-EpCam therapies are now being used in clinical trials. Thus, it is of interest to know which tumor types express or overexpress this protein, and in what frequency. We therefore analyzed EpCam expression by immunohistochemistry on a tissue microarray containing 3900 tissue samples of 134 different histological tumor types and subtypes. EpCam expression was detected in 98 of 131 tumor categories. At least a weak EpCam expression in >10% of tumors was observed in 87 of 131 different tumor categories. Adenocarcinomas of the colon (81%) and pancreas (78%), as well as hormone-refractory adenocarcinomas of the prostate (71%), were identified as particularly promising therapy targets with a high fraction of strongly positive tumors. Most soft-tissue tumors and all lymphomas were EpCam negative. It is concluded that anti-EpCam therapies, if proven to be successful, will have broad applications in a wide variety of carcinomas.

Adenocarcinoma↗
PubMed2003

Tumor-specific glycosylation of the carcinoma-associated epithelial cell adhesion molecule EpCAM in head and neck carcinomas.

The tissue-specific glycosylation of the carcinoma (CA)-associated antigen epithelial cell adhesion molecule (EpCAM) was studied in 60 patients suffering from head and neck CAs, and 26 pairs of autologous healthy thyroid and CA biopsies. EpCAM was glycosylated in all tumor samples in which its expression was detectable (73%). Additionally, in 80.7% of patients, tumor-derived EpCAM was heavily glycosylated while EpCAM derived from autologous thyroid was not (76.2%) or weakly (23.8%). Four cases showed a similar glycosylation pattern (15.3%) and one case displayed a reverse pattern (3.8%). Additionally, the expression and glycosylation of EpCAM were assessed in tumor adjacent and distant tissue. EpCAM was glycosylated in tumor-adjacent while it was not or only weakly expressed in tumor distant tissue where it was unglycosylated. Thus, EpCAM is differentially glycosylated in healthy tissue and tumor cells of the head and neck area.

Adult↗
PubMed2007

EpCAM (CD326) finding its role in cancer.

Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growth-promoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future.

Antigens, Neoplasm↗
PubMed2001

Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and LewisY antigen expression.

MoAbs against tumour-associated antigens (TAA) may be useful for the treatment of colorectal cancer. Since an increased expression of TAA may lead to enhanced antibody-dependent cellular cytotoxicity we examined whether the cytokines IL-2, IL-4, IL-6, IL-10, IL-12, interferon-alpha (IFN-alpha), IFN-gamma, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and tumour necrosis factor-alpha can influence EpCAM and LewisY expression on the surface of the colorectal carcinoma cell lines HT29, LoVo and SW480. We found that only IFN-alpha increased significantly whereas IL-4 decreased both EpCAM and LewisY expression. IFN-gamma significantly increased LewisY expression only. When tumour cells were treated with MoAb, the LewisY-specific MoAb BR55-2 down-regulated LewisY antigen expression, whereas MoAb 17-1A, which binds to EpCAM, up-regulated this TAA after 3 days of culture. The cytokines IFN-alpha or IFN-gamma combined with MoAb 17-1A enhanced further slightly the expression of EpCAM. In additional experiments with chemotherapeutic drugs commonly used for the treatment of colorectal cancer, we found that 5-fluorouracil, mitomycin-C and oxaliplatin up-regulated EpCAM and LewisY antigen expression. Raltitrexed enhanced LewisY and down-regulated EpCAM expression, whereas CPT-11 had no influence at all. The highest expression for EpCAM on HT29 cells was achieved by the combination of IFN-alpha, 5-fluorouracil and MoAb 17-1A. Our results may be useful for defining combinations of biological and chemotherapeutic drugs for the treatment of colorectal cancer. Further trials should evaluate to what extent these combinations enhance antibody-dependent cellular cytotoxicity.

Adjuvants, Immunologic↗