Adjuvant Therapy with Edrecolomab versus Observation in Stage II Colon Cancer: A Multicenter Randomized Phase III Study*

Hartung, G.; Hofheinz, R.D.; Dencausse, Y.; Sturm, J.; Kopp‐Schneider, Annette; Dietrich, Georg; Fackler-Schwalbe, I.; D, Bornbusch; Gonnermann, Michael; Wojatschek, C.; Lindemann, Walter; Eschenburg, Henning; Jost, Kirsten; Edler, Lutz; Hochhaus, Andreas; Queißer, W.

doi:10.1159/000084595

Cited by 47 publications

(37 citation statements)

References 19 publications

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“…This well-tolerated murine IgG2a antibody, which was temporarily marketed in Germany, showed a significant increase in overall survival of colorectal cancer patients in the adjuvant setting in two out of four trials (Riethmüller et al, 1994(Riethmüller et al, , 1998Hempel et al, 2000;Punt et al, 2002;Hartung et al, 2005). The speaker concluded that despite a very benign safety profile of edrecolomab, its short half-life, rapid neutralisation by a mouse-anti-human antibody response, and a borderline clinical activity asks for development of an improved mAb, ideally of human nature.…”

Section: Epcam-directed Immunotherapies Under Developmentmentioning

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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Section: Epcam-directed Immunotherapies Under Developmentmentioning

confidence: 99%

EpCAM (CD326) finding its role in cancer

Baeuerle¹,

2007

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“…The first antibody used in passive immunotherapy was edrecolomab, a murine IgG2a antibody targeting Ep-CAM (Sears et al, 1984;Riethmuller et al, 1994). The therapeutic effect of this antibody administered alone or in combination with chemotherapy or GM-CSF (Mellstedt et al, 2000) was not conclusive, but it showed a very benign safety profile (Fields et al, 2002;Punt et al, 2002;Hartung et al, 2005). To reduce immunogenicity and enhance antibodydependant cytotoxicity, complement dependant cytotoxicity and serum half-life, humanised antibodies ING-1 (de Bono et al, 2004), 3622W94 (Abdullah et al, 1999;Martin et al, 1999) and fully human IgG1 antibody MT201 (adecatumumab) (Naundorf et al, 2002;Brischwein et al, 2005) were developed.…”

Section: Discussionmentioning

confidence: 99%

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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“…The clinical testing showed the chimeric construct increased mononuclear cell-mediated ADCC and prolonged half-life than the murine mAb. In addition, it develops no human anti-mouse antibodies (Hartung et al, 2005).…”

Section: Targets In Solid Tumorsmentioning

confidence: 99%