Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies.

Herlyn, Meenhard; Steplewski, Zenon; Herlyn, Dorothee; Koprowski, Hilary

doi:10.1073/pnas.76.3.1438

Cited by 556 publications

(264 citation statements)

References 11 publications

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“…In his introductory remarks, G Riethmueller (Munich, Germany) pointed out that the first human tumour-associated antigen identified with monoclonal antibodies (mAb) was in fact EpCAM or 17-1A antigen (Herlyn et al, 1979). Moreover, the first monoclonal antibody ever applied for human cancer therapy was murine mAb 17-1A recognising EpCAM (Sears et al, 1982(Sears et al, , 1984.…”

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confidence: 99%

EpCAM (CD326) finding its role in cancer

Baeuerle¹,

2007

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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 growthpromoting 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.

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confidence: 99%

EpCAM (CD326) finding its role in cancer

Baeuerle¹,

2007

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“…This choice was supported by the availability of human colorectal cancer cell lines that can form tumor xenografts in immunodeficient mice, allowing evaluation of anti-cancer PCALs in preclinical studies. Furthermore, the clinically used [Riethmuller et al, 1998] anticolorectal cancer murine MAb, CO17-1A [Herlyn et al, 1979[Herlyn et al, , 1980, is available for comparative studies.…”

Section: Prototypic Pcals To Human Colorectal Cancermentioning

confidence: 99%

“…The FDAapproved MAbs include: Rituxan 1 , a chimeric anti-CD20 antibody approved for the treatment of non-Hodgkin's lymphoma; Campath 1 , a humanized anti-CD52 antibody approved for treatment of chronic lymphocytic leukemia; Herceptin 1 , a humanized anti-HER2/neu antibody approved for treatment of breast cancer; Erbitux 1 , a chimeric anti-endothelial growth factor receptor (EGFR) antibody and Avastin 1 , a humanized anti-vascular endothelial growth factor (VEGF) antibody, both approved for the treatment of metastatic colorectal cancer; radiolabeled murine anti-CD20 antibodies Zevalin 1 and Bexxar 1 , approved for the treatment of non-Hodgkin's lymphoma; and Mylotarg 1 , a humanized anti-CD33 antibody linked to a cytotoxic antibiotic, approved for the treatment of acute myeloid leukemia. In addition, Panorex (CO17-1A [Herlyn et al, 1979[Herlyn et al, , 1980), a murine MAb reactive with the tumor associated antigen Ep-CAM-was approved in Germany for the treatment of colorectal cancer [Riethmuller et al, 1994[Riethmuller et al, , 1998]. Although remissions have been noted using MAbs for cancer treatment, most were only temporary [Divgi and Larson, 1995;Riethmuller et al, 1998;Ben-Efraim, 1999;Macdonald, 1999;Normanno et al, 2003].…”

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Recombinant polyclonal antibodies for cancer therapy

Sharon¹,

Liebman²,

Williams³

2005

J of Cellular Biochemistry

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Although monoclonal antibodies are increasingly used for cancer therapy, remissions are only temporary due to emergence of tumor cell escape variants that are no longer affected by the antibody. The emergence of escape variants could be minimized by multi-targeting of tumor cells with polyclonal antibodies, which would also be more efficient than monoclonal antibodies at mediating effector functions for target destruction. A technology for generating recombinant polyclonal antibodies for cancer therapy has been developed based on the construction and selection of tumor-reactive Fab phage display libraries. The selected Fabs are mass-converted to full-length polyclonal antibody libraries (PCALs) of any isotype and any species. Prototypic PCALs generated against human colorectal cancer cell lines showed that libraries of diverse recombinant antibodies, enriched for reactivity to the cancer cells compared to normal human cells, can be obtained. The success of recombinant polyclonal antibodies as cancer therapeutics will depend on the ability to generate, characterize, and mass-produce PCALs with high ratios of cancer-to-normal reactivities that crossreact with many cancers of the same type.

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“…Epithelial cell adhesion molecule was discovered as one of the first tumour-associated antigens by immunising mice with human colon cancer cells followed by analysis of tumour-specific monoclonal antibodies (Herlyn et al, 1979;Sears et al, 1982). Epithelial cell adhesion molecule was then found to be expressed at a high level and frequency not only on colon cancer tissues but on most human adenocarcinomas as well as on squamous cell carcinomas (Quak et al, 1990).…”

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Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

et al. 2006

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Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n ¼ 1186) of colon, 90.7% of gastric (n ¼ 473), and 87.2% of prostate cancers (n ¼ 414), and in 63.9% of lung cancers (n ¼ 1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (Po0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P ¼ 0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression.

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Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies.

Cited by 556 publications

References 11 publications

EpCAM (CD326) finding its role in cancer

EpCAM (CD326) finding its role in cancer

Recombinant polyclonal antibodies for cancer therapy

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

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