Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EPCAM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2003

Human tumor-derived heat shock protein 96 mediates in vitro activation and in vivo expansion of melanoma- and colon carcinoma-specific T cells.

Heat shock proteins (hsp) 96 play an essential role in protein metabolism and exert stimulatory activities on innate and adaptive immunity. Vaccination with tumor-derived hsp96 induces CD8(+) T cell-mediated tumor regressions in different animal models. In this study, we show that hsp96 purified from human melanoma or colon carcinoma activate tumor- and Ag-specific T cells in vitro and expand them in vivo. HLA-A*0201-restricted CD8(+) T cells recognizing Ags expressed in human melanoma (melanoma Ag recognized by T cell-1 (MART-1)/melanoma Ag A (Melan-A)) or colon carcinoma (carcinoembryonic Ag (CEA)/epithelial cell adhesion molecule (EpCAM)) were triggered to release IFN-gamma and to mediate cytotoxic activity by HLA-A*0201-matched APCs pulsed with hsp96 purified from tumor cells expressing the relevant Ag. Such activation occurred in class I HLA-restricted fashion and appeared to be significantly higher than that achieved by direct peptide loading. Immunization with autologous tumor-derived hsp96 induced a significant increase in the recognition of MART-1/Melan-A(27-35) in three of five HLA-A*0201 melanoma patients, and of CEA(571-579) and EpCAM(263-271) in two of five HLA-A*0201 colon carcinoma patients, respectively, as detected by ELISPOT and HLA/tetramer staining. These increments in Ag-specific T cell responses were associated with a favorable disease course after hsp96 vaccination. Altogether, these data provide evidence that hsp96 derived from human tumors can present antigenic peptides to CD8(+) T cells and activate them both in vitro and in vivo, thus representing an important tool for vaccination in cancer patients.

Antigen Presentation↗
PubMed2002

Micrometastatic tumor detection in patients with head and neck cancer: a preliminary report.

OBJECTIVE: To apply a new immunocytochemistry (ICC) assay to peripheral blood samples for micrometastatic circulating tumor cell detection in patients with head and neck squamous cell cancer (HNSCC). DESIGN: The ICC assay uses established monoclonal antibodies that bind to tumor-associated antigens combined with an enrichment system that uses positive selection with anti-human epithelial antigen (EpCAM antibody) to detect circulating tumor cells. SUBJECTS: Eighteen consecutive patients newly diagnosed as having HNSCC are described. RESULTS: Of the 18 patients, 8 (44%) demonstrated circulating tumor cells using the ICC assay. The numbers of patients positive for circulating tumor cells per stage are as follows: stage I, 1 of 1; stage II, 0 of 2; stage III, 2 of 5; stage IV, 5 of 6; and unknown stage, 0 of 4. The numbers of patients positive for circulating tumor cells per location are as follows: oral cavity, 1 of 2; oropharynx, 3 of 4; glottic area, 3 of 5; supraglottic area, 1 of 3; and unknown primary 0 of 4. CONCLUSIONS: Circulating tumor cells were identified in almost half of the patients using the ICC assay. In a literature review, we were not able to identify previous reports of circulating tumor cell detection in patients with HNSCC from peripheral blood samples using ICC or identify any study that has attempted to quantify circulating tumor cell levels. Although the clinical implications of circulating tumor cells in micrometastatic tumor detection in patients with HNSCC are still unknown, they may be significant. Long-term follow-up may help elucidate the patients in whom conventional treatment may fail and, thus, those who may benefit from different treatment; it may also assist with the detection of recurrence with a simple blood collection.

Adult↗
PubMed2002

Enhancement of the complement activating capacity of 17-1A mAb to overcome the effect of membrane-bound complement regulatory proteins on colorectal carcinoma.

Adjuvant immunotherapy with 17-1A mAb directed against colorectal carcinoma is found to be effective in patients. However, 52 % of the patients treated with mAb 17-1A showed recurrence within 7 years. This high recurrence rate might be due to inhibition of complement activation by membrane-bound complement regulatory proteins (mCRP). The effect of these complement regulatory proteins might be reduced by blocking mCRP, or be overcome by activating more complement at the tumor cell membrane. In this study the complement-activating capacity of the 17-1A mAb was enlarged by conjugating it to cobra venom factor (CVF) or C3b. The most important C3 regulatory protein, CD55, was blocked using a bispecific mAb directed against the 17-1A / Ep-CAM antigen and CD55. Up to a 13-fold increase in C3 deposition was observed due to 17-1A-CVF and 17-1A-C3b, as compared to 17-1A. CD55 was shown to partly inhibit complement activation by these conjugates. The effect of the bispecific anti-17-1A / Ep-CAM*anti-CD55 mAb was compared with 17-1A conjugates with CVF or C3, and bispecific mAb were shown to be equally or more efficient in complement activation than the 17-1A-CVF or 17-1A-C3b conjugates. Therefore, 17-1A conjugates and anti-17-1A / EpCAM*anti-CD55 bispecific mAb may be promising immunotherapeutic agents for patients with colorectal cancer.

Animals↗
PubMed2002

Use of magnetic enrichment for detection of carcinoma cells in fluid specimens.

BACKGROUND: Ascites fluid or a pleural effusion are common events in metastatic carcinoma, but they also can be associated with several other medical conditions. The standard for determination of malignancy in these situations is cytologic evaluation of these fluids. Although this method is frequently successful, there are times when it fails, even when the patient has a malignancy, either because of insufficient cells in the fluid or for other reasons. This study addresses this problem taking advantage of the recent advances in technology for detection of rare epithelial cells in liquid specimens. METHODS: The authors examined fluid specimens from 59 patients to determine the frequency of recovery of epithelial cells compared with that achieved by conventional cytopathology. The Dynal CELLection Epithelial Enrich (Dynal AS, Oslo, Norway) method was used. This method is based on immunomagnetic selection of cells binding to EpCAM antibodies. Carcinoma cells were confirmed by morphology and, when there was sufficient material, by E-cadherin staining. RESULTS: Grouping the cases by cytologic diagnosis, the authors found malignant cells using the cell enrichment assay in 11 of 12 malignant cases, 2 of 5 atypical cases, and 3 of 42 negative cases. Further investigations were conducted on the five cases that were cytologically negative or atypical but yielded epithelial cells after immunomagnetic enrichment. Four cases ultimately were proven malignant by other methods and one had incomplete follow-up. CONCLUSIONS: The new methods available for epithelial cell enrichment in liquids may be used successfully on cytologic fluid specimens and may lead to increased sensitivity for detection of malignancy, and consequently more accurate staging.

Ascites↗
PubMed2005

Trifunctional bispecific antibody-induced tumor cell lysis of squamous cell carcinomas of the upper aerodigestive tract.

BACKGROUND: The trifunctional bispecific antibody Removab (tbAB) bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune-cell inducing tumor cell lysis. tbAB-induced tumor cytotoxicity was assessed in an autologous human ex vivo system. METHODS: One hundred forty tumor samples and autologous peripheral blood mononuclear cells from a total of 36 patients with head and neck squamous cell carcinomas (HNSCCs) were incubated on a chicken embryo chorioallantois membrane with Removab. Tumor cells coincubated with cisplatin or cell culture medium served as positive and negative controls. Tumor cell lysis was assessed by acridine orange staining or by fluorescence-activated cell sorting of propidium iodide-marked cells after 24 and 48 hours (T24/T48) coincubation. RESULTS: Coincubation of HNSCC cells with tbAB and autologous peripheral blood mononuclear cells resulted in a 49% +/- 6% decrease of viable cells at T24 (p < .005) and in a decrease of 56% +/- 8% at T48 (p < .005) compared with the control. The tumor cytotoxicity was similar to that of cisplatin (49% +/- 7% decrease at T24 and 49% +/- 8% at T48). CONCLUSION: In an autologous human ex vivo system, the tbAB-induced tumor cell lysis was comparable to that by cisplatin.

Antibodies, Bispecific↗
PubMed1999

Immortalized intrahepatic mouse biliary epithelial cells: immunologic characterization and immunogenicity.

Nonsuppurative destructive cholangitis (NSDC), a process of T-cell-mediated destruction of biliary epithelia observed in primary biliary cirrhosis (PBC), graft-versus-host disease (GVHD), and hepatic allograft rejection (HAR), also occurs in the B10. D2-->BALB/c model of GVHD. To advance studies of immunopathogenesis in this murine model, we immortalized 4 BALB/c intrahepatic biliary epithelial cell (BEC) lines as a reliable source of target cells. Freshly isolated BEC, as well as each cell line, expressed cytokeratin-19 (CK-19), epithelial cell adhesion molecule (EPCAM) and cystic fibrosis transmembrane conductance regulator (CFTR). None expressed albumin. Immortalized cells also expressed SV40 large T antigen. Class I major histocompatibility complex (MHC) was expressed by >97% of immortalized cells, while class II MHC and intercellular adhesion molecule-1 (ICAM-1) expression ranged from 0% to 13% and 14% to 74%, respectively. Interferon gamma (IFN-gamma) induced aberrant class II MHC expression and increased expression of ICAM-1. Variable proportions of immortalized cells expressed B7-1/B7-2 molecules and FAS. IFN-gamma significantly reduced B7-1 expression in some lines and significantly increased B7-2 expression in others. Allografts of freshly isolated and immortalized BEC injected into subscapular fat pads spontaneously formed duct-like structures. Inflammation was absent in BALB/c recipients. In contrast, inflammatory lesions in B10.D2 recipients were reminiscent of NSDC. Our results indicate that BALB/c-immortalized intrahepatic biliary cells: 1) retain the phenotype of mouse BEC; 2) can be induced to express aberrant class II MHC and increased ICAM-1; 3) express costimulatory B7-1/B7-2 molecules and FAS; and 4) spontaneously form duct-like structures after in vivo injection that are immunogenic in B10.D2 mice. These cell lines should facilitate future studies of the immunopathogenesis of NSDC in the B10. D2-->BALB/c murine model.

Animals↗
PubMed2004

Target cell-restricted and -enhanced apoptosis induction by a scFv:sTRAIL fusion protein with specificity for the pancarcinoma-associated antigen EGP2.

The apparent tumor selective apoptosis-inducing activity of recombinant soluble TNF-related apoptosis-inducing ligand (TRAIL) has aroused much interest for use in clinical application. However, to exploit fully its therapeutic potential, the characteristics of both the TRAIL receptor system and soluble TRAIL (sTRAIL) should be taken into account: first, the widespread expression of the various TRAIL receptors throughout the human body; second, the differential binding affinities and crosslinking requirements of the agonistic receptors TRAIL-R1 and TRAIL-R2; and third, the solution behavior of particular sTRAIL preparations. Therefore, we constructed a novel TRAIL fusion protein, designated scFvC54:sTRAIL, comprising the human scFv antibody fragment C54 genetically linked to the N-terminus of human sTRAIL. The scFvC54:sTRAIL fusion protein was designed to induce apoptosis by crosslinking of agonistic TRAIL receptors only after specific binding of scFvC54:sTRAIL to the abundantly expressed carcinoma-associated cell surface antigen EGP2 (alias EpCAM). Target antigen-restricted apoptosis induction was demonstrated for various EGP2-positive tumor cells and could be inhibited by an EGP2 competing antibody. Target antigen binding converted soluble scFvC54:sTRAIL into a membrane-bound form of TRAIL that was capable of signaling apoptosis not only through TRAIL-R1 but also through TRAIL-R2. Size-exclusion fast protein liquid chromatography (FPLC) indicated that scFvC54:sTRAIL was produced as stable and homogeneous trimers in the absence of detectable TRAIL aggregates. The favorable characteristics of the scFvC54:sTRAIL fusion protein potentially reduce the amount of sTRAIL required for antitumor activity and may be of value for the treatment of various human carcinomas.

Animals↗
PubMed2001

Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity.

High-dose chemotherapy (HDC) with autologous bone marrow or peripheral stem cell transplantation is discussed as one option to treat the extensive stage of a variety of tumors. Effective methods to eliminate contaminating tumor cells from human bone marrow or stem cell grafts may improve the outcome of the patients. We investigated 3 recombinant bispecific single-chain antibodies (bscAbs) directed against 17-1A (EpCAM), c-erbB-2 (HER-2/neu) and LeY on the one and CD3 on the other binding site for their ability to induce lysis of epithelial tumor cells by retargeting autochthonous T lymphocytes present in bone marrow mononuclear cells (BMMC) and in peripheral stem cell mononuclear cells (PSMC). The bscAbs showed remarkable specific lysis of different epithelial tumor cell lines with BMMCs as well as with PSMCs as effector cells. Investigation of the alpha 17-1A-alpha CD3 bscAb revealed a significant correlation between the percentage of CD3(+) cells present in the BMMCs and the rate of lysis as well as the absence of detrimental effects on the viability of hematopoietic progenitor cells as determined by colony-forming unit assays (CFUs). Our results indicate that recombinant bispecific single-chain antibodies could be new tools for purging of human bone marrow and peripheral stem cell grafts from contaminating epithelial cancer cells for patients receiving autologous stem cell transplantation after HDC.

Antibodies, Bispecific↗
PubMed2005

Immunotherapy of malignant ascites with trifunctional antibodies.

A new class of intact bispecific antibodies shows unmet effector qualities by activation of not only T cells but also simultaneous activation of Fcgamma receptor type I/III+ cells (macrophages, NK-cells and DC). These trifunctional antibodies (trAb) lead to efficient specific killing of targeted tumor cells without any pre- or co-stimulation. This concept was investigated in vivo in patients with malignant ascites in a clinical situation that allowed monitoring of tumor cell elimination and correlation with clinical effects. In a prospective study, 8 patients with malignant ascites due to peritoneal carcinomatosis were treated with intraperitoneal application of trAb, which bound either the EpCAM- or Her2/neu-antigen on tumor cells. Treatment consisted of 4-6 applications within 9-23 days with a total amount of 145-940 microg. Seven of eight patients required no further paracentesis during follow-up or until death with a mean paracentesis-free interval of 38 weeks (median = 21.5, range = 4-136). Tumor cell monitoring showed a complete elimination of tumor cells in ascites already at total doses as low as 40-140 microg. Clinical response with disappearance of ascites accumulation was seen in all patients, which was correlated with elimination of tumor cells (p = 0.0014). Severe adverse events were not observed. Clinically relevant side effects were fever, moderate abdominal pain and skin reactions. Intraperitoneal immunotherapy with trAb showed convincing efficacy in patients with malignant ascites. This treatment offers new therapeutic options for patients with peritoneal carcinomatosis.

Ascites↗
PubMed2006

Multiplex detection of surface molecules on colorectal cancers.

A technique of fluorescence multiplexing is described for analysis of the plasma membrane proteome of colorectal cancer cells from surgically resected specimens, enabling detection and immunophenotyping when the cancer cells are in the minority. A single-cell suspension was prepared from a colorectal tumour, and the mixed population of cells was captured on a CD antibody microarray. The cancer cells were detected using a fluorescently tagged antibody for carcinoembryonic antigen (CEA-Alexa647) or epithelial cell adhesion marker (EpCAM-Alexa488). Using this multiplexing procedure, dot patterns from colorectal cancers were distinct from those of adjacent normal tissue. Subtraction of the expression levels for each antigen from normal tissue from those for the cancer shows differential expression in the cancer of CD66c, CD15s, CD55, CD45, CD71, CD45RO, CD11b and CEA, in descending order. Cells captured on the same microarray were also labelled with fluorescent CD3-phycoerythrin antibody revealing the presence of tumour-infiltrating lymphocytes. The immunophenotypes of T lymphocytes from the tumour samples showed differential expression of HLA-DR, TCR alpha/beta, CD49d, CD52, CD49e, CD5, CD95, CD28, CD38 and CD71, in descending order. Fluorescence multiplexing of mixed cell populations captured on a single antibody microarray enables expression profiling of multiple sub-populations of cells within a tumour sample.

CD4 Antigens↗
PubMed2005

Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes.

This study was designed to determine the characteristics of tumour cell-derived microvesicles (TMV) and their interactions with human monocytes. TMV were shed spontaneously by three different human cancer cell lines but their release was significantly increased upon activation of the cells with phorbol 12-myristate 13-acetate (PMA). TMV showed the presence of several surface determinants of tumour cells, e.g. HLA class I, CD29, CD44v7/8, CD51, chemokine receptors (CCR6, CX3CR1), extracellular matrix metalloproteinase inducer (EMMPRIN), epithelial cell adhesion molecule (EpCAM), but their level of expression differed from that on cells they originated from. TMV also carried mRNA for growth factors: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-8 (IL-8) and surface determinants (CD44H). TMV were localized at the monocytes surface following their short exposure to TMV, while at later times intracellularly. TMV transferred CCR6 and CD44v7/8 to monocytes, exerted antiapoptotic effect on monocytes and activated AKT kinase (Protein Kinase B). Thus, TMV interact with monocytes, alter their immunophenotype and biological activity. This implicates the novel mechanism by which tumour infiltrating macrophages may be affected by tumour cells not only by a direct cell to cell contact, soluble factors but also by TMV.

Adenocarcinoma↗
PubMed2026

Integrated bulk and single-cell RNA sequencing reveals a prognostic neuro-mimicry signature in papillary thyroid carcinoma.

BACKGROUND: Cancer cells can acquire neuron-like characteristics ("neural mimicry") to promote progression. However, the role of specific ion channel genes in Papillary Thyroid Carcinoma (PTC) and their clinical significance remains unclear. METHODS: We included transcriptomic data from 521 PTC patients in the TCGA cohort. A neuron-specific gene set was used to screen for potential targets. We constructed a prognostic model using LASSO logistic regression. To verify the cellular origin of the signature, we performed single-cell RNA sequencing (scRNA-seq) analysis on the GSE184362 dataset. RESULTS: We established an 8-gene signature involving KCNN4, KCNN1, KCNT2, SNAP25, KCNK16, GABRG1, GABRG2, and GABRB2. The model demonstrated good predictive performance for lymph node metastasis, with an AUC of 0.721 (95% CI 0.677-0.765). Single-cell analysis of seven integrated tumor samples (N&#x2009;=&#x2009;65,744 cells) confirmed that GABRB2 was specifically enriched in malignant thyrocytes (EPCAM+/KRT18+) at 200-fold higher detection rates than immune cells (20.0% vs. 0.1%, P&#x2009;&#x2248;&#x2009;0), supporting tumor-intrinsic neural mimicry. High-risk patients showed immunosuppressive features with altered immune cell infiltration patterns. CONCLUSION: This study identifies a malignant cell-intrinsic signature for predicting PTC prognosis. Validated by single-cell data, our findings suggest that targeting ion channels may represent a potential therapeutic strategy for modulating neuro-immune interactions in thyroid cancer, pending experimental validation.

GABRB2↗
PubMed2004

Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas.

Despite some success in the treatment of colorectal carcinomas, novel rational therapies targeting specific cancer-related molecules are under development and urgently needed. These approaches need careful preclinical evaluation in models that closely mirror the clinical situation. Therefore, we established a panel of 15 xenotransplantable tumours directly from fresh surgical material. We showed that both the histology and expression of tumour-associated markers (Epithelial Cell Adhesion molecule (EpCAM), E-cadherin, carcinoembryonic antigen (CEA)) could be maintained during passaging in nude mice. Xenotransplanted tumours were characterised for chemosensitivity and revealed a response rate of 5/15 (33%) for 5-fluorouracil (5-FU), 15/15 (100%) for irinotecan and 8/14 (57%) for oxaliplatin. 5 patients out of 15 were treated with cytostatics because of synchronous metastases. The response to chemotherapy in these patients coincided very closely with the response of the individual xenografts. All of the xenografts expressed the proliferation marker Ki67 and the nuclear enzyme, Topoisomerase IIalpha (Topo IIalpha) at the protein level. Most of the xenografts also expressed the tumour suppressor, p53 (9/14) and the nuclear enzyme Topoisomerase Ialpha (Topo Ialpha) (13/14) at the protein level. Interestingly, the presence of a K-ras mutation in codon 12 (5/15 xenografts) coincided with a low response rate towards oxaliplatin. This observation needs further confirmation using a larger number of tumours. In conclusion, we were able to establish transplantable xenografts suitable to mimic the clinical situation. These well characterised models are useful tools for the preclinical development of novel therapeutic approaches and for investigating translational research aspects.

Animals↗
PubMed2005

Bi-specific immunomagnetic enrichment of micrometastatic tumour cell clusters from bone marrow of cancer patients.

Metastasis-the spread of tumour cells from a primary lesion to distant organs-is the main cause of cancer-related death, and bone marrow (BM) is a frequent site for the settlement of disseminated tumour cells. Many BM samples harbour isolated tumour cells, whereas tumour cell clusters, as the potential precursors of solid distant metastases, are rarely detected after current enrichment procedures. We have analysed BM samples from 43 patients with carcinomas of the breast, colon and ovaries; 41 of these patients had no clinical signs of overt metastases (stage M0). Tumour cells in BM were enriched with immunomagnetic beads coupled to monoclonal antibodies against both EpCAM and HER2/neu. After enrichment, tumour cells were identified by immunostaining with the anti-cytokeratin antibody A45-B/B3. In total, 886 CK-positive cells were detected in 16 (35%) samples after immunomagnetic enrichment as compared to 34 cells in 9 (21%) samples using Ficoll density centrifugation previously used as the standard enrichment technique. Most remarkably, clusters of 2 to 10 CK-positive cells were found in 75% of CK-positive samples enriched by immunobeads, whereas no CK-positive cell clusters were detected after Ficoll enrichment. The method described offers an excellent tool for the enrichment of micrometastatic tumour cell clusters; these clusters may represent the initial stage of development from a single disseminated tumour cell towards an overt metastasis.

Bone Marrow Neoplasms↗
PubMed1997

Identification of potential HLA-A *0201 restricted CTL epitopes derived from the epithelial cell adhesion molecule (Ep-CAM) and the carcinoembryonic antigen (CEA).

The altered expression pattern of the Epithelial Cell Adhesion Molecule (Ep-CAM) and the Carcinoembryonic Antigen (CEA) on tumor cells of epithelial origin as compared to normal epithelia may permit T cells to preferentially recognize and lyse these tumor cells. The binding affinity for human leucocyte antigen A2.1 (HLA-A*0201) and the capacity to form stable peptide-major histocompatibility complex (MHC) interactions with this molecule were tested for 410 Ep-CAM-derived sequences, including an overlapping set of 9 amino-acid-long peptides, and 73 CEA-derived peptides fulfilling the HLA-A*0201 motif. Peptides with a high binding affinity and a low peptide-MHC dissociation rate were subsequently tested for their immunogenicity in HLA-A*0201Kb transgenic mice. One Ep-CAM-derived peptide and 1 CEA-derived peptide were able to reproducibly induce peptide-specific cytotoxic T cells (CTL) in these mice. This indicates that EpCAM and CEA are potential target antigens for CTL-mediated immunotherapy of epithelial cancers.

Animals↗
PubMed1999

Two proteins share immunological epitopes on the tumor-associated antigen 17-1A.

The mouse monoclonal antibody (mAb) 17-1A which recognizes the tumor-associated antigen 17-1A (also called EGP-40 or EpCAM) was successfully used in adjuvant therapy for colorectal carcinoma. In the 17-1A antigen analysis, we isolated not only a protein of 33 kDa (P33) which was reported as the tumor associated antigen 17-1A, but also a protein of 65 kDa (P65) using affinity chromatography from cell lysates of HCT, and another protein of 50 kDa (P50) from lysates of human colorectal tumor tissues. The mAbs 17-1A and M79 (mAb M79 recognizes a different epitope on the 17-1A antigen) both could bind P33 and P50, but only M79 bound to P65 in an enzyme-linked immunosorbant assay (ELISA). These results indicate that P33 and P50 share at least two epitopes, and a common immunological epitope exists among P33, P50 and P65, suggesting that the two new proteins (P50 and P65) are related to the tumor-associated antigen 17-1A.

Animals↗
PubMedDate not supplied

Anti-idiotypic antibody and recombinant antigen vaccines in colorectal cancer patients.

The colorectal carcinoma (CRC)-associated GA733 antigen (also known as CO17-1A, KS1-4, KSA or EpCAM) has been the target of a phase II/III randomized trial of passive immunotherapy with monoclonal antibody CO17-1A and phase I active immunotherapy trials with polyclonal anti-idiotypic antibodies mimicking the CO17-1A or GA733 epitope on the antigen. The CO17-1A antigen was molecularly cloned and the extracellular domain expressed in baculovirus (BV) GA733-2E. Whereas, anti-idiotypic antibody mimics a single epitope on the antigen, BV GA733-2E expresses multiple potentially immunogenic epitopes. In animals, the immunogenicity of BV GA733-2E in aluminum hydroxide was superior to that of anti-idiotype in the same adjuvant. Here, we compared the immunogenicity of anti-idiotypic antibody and GA733-2E antigen in CRC patients. These studies indicate that the antigen is superior to the anti-idiotype antibody in inducing humoral and cellular immunity in CRC patients.

Antibodies, Anti-Idiotypic↗
PubMed1998

Prognostic significance of micrometastatic bone marrow involvement.

The present review focuses on the methodology and clinical significance of new diagnostic approaches to identify micrometastatic breast cancer cells present in bone marrow (BM), as a frequent site of overt metastases. Using monoclonal antibodies (mAbs) to epithelial cytokeratins (CK) or tumor-associated cell membrane glycoproteins, individual carcinoma cells can be detected on cytologic BM preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of these immunostained cells is prognostically relevant with regard to relapse-free and overall survival. The current interest in autologous bone marrow transplantation in patients with solid tumors further underlines the need for screening methods that allow the detection of minute numbers of residual tumor cells in the transplant. Although the development of new molecular detection methods based on the amplification of a marker mRNA species by the polymerase chain reaction technique is a very exciting area of research, the clinical significance of this approach needs to be demonstrated in prospective studies. The immunocytochemical assays may be, therefore, used to improve tumor staging with potential consequences for adjuvant therapy. Another promising clinical application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The extremely low frequency of BM tumor cells greatly hampers approaches to obtain more specific information on their biological properties. The available data indicate that these cells represent a selected population of cancer cells which, however, still express a considerable degree of heterogeneity with regard to the expression of MHC class I antigens, adhesion molecules (EpCAM), growth factor receptors (EGF receptor, erb-B2, transferrin receptor), or proliferation-associated markers (Ki-67, p120). Regardless of the detection technique applied, there is an urgent demand for large multicentre trials, in which standardized methods are related to specified clinical outcomes.

Bone Marrow↗