Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma

Riethmüller, Gert; Gruber, Rudolf; Schneider-Gädicke, E.; Schlimok, Günter; Raab, R.; Pichlmayr, R.; Pichlmaier, H.; Schmiegel, Wolff; Buggisch, Peter; Höffken, K.; Hirche, H.; Pichimayr, R.; Witte, Jens

doi:10.1016/s0140-6736(94)92398-1

Cited by 591 publications

(228 citation statements)

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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%

“…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. In 1994, mAb17-1A (later named edrecolomab and Panorex s ) was also the first to show clinical efficacy in a human cancer indication in terms of prolonged overall survival (Riethmüller et al, 1994). It was then almost 30 years after the first generation of an EpCAM-specific monoclonal antibody that an international community gathered in Bavaria to discuss for the first time the most recent advances in the field of EpCAM research and clinical utility.…”

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confidence: 99%

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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%

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confidence: 99%

EpCAM (CD326) finding its role in cancer

Baeuerle¹,

2007

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“…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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confidence: 99%

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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“…In an academically sponsored phase III trial, monotherapy with edrecolomab was shown to increase the overall survival after 10 years by 32% in patients with resected colorectal carcinoma at the Dukes C stage. 11,12 A recent, much larger phase III trial has shown that edrecolomab monotherapy was inferior after a 3-year observation period to the meanwhile introduced chemotherapy with 5-fluorouracil/leucovorin. 13 This led to the withdrawal of edrecolomab's market approval.…”

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confidence: 99%

In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment

Naundorf

Preithner

Mayer

et al. 2002

Intl Journal of Cancer

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In our study, a novel, fully human, recombinant monoclonal antibody of the IgG1 isotype, called MT201, was characterized for its binding properties, complement-dependent (CDC) and antibody-dependent cellular cytotoxicity (ADCC), as well as for its in vivo antitumor activity in a nude mouse model. MT201 was found to bind its target, the epithelial cell adhesion molecule (Ep-CAM; also called 17-1A antigen, KSA, EGP-2, GA733-2), with low affinity in a range similar to that of the clinically validated, murine monoclonal IgG2a antibody edrecolomab (Panorexா). MT201 exhibited Ep-CAM-specific CDC with a potency similar to that of edrecolomab. However, the efficacy of ADCC of MT201, as mediated by human immune effector cells, was by 2 orders of magnitude higher than that of edrecolomab. Addition of human serum reduced the ADCC of MT201 while it essentially abolished ADCC of edrecolomab within the concentration range tested. In a nude mouse xenograft model, growth of tumors derived from the human colon carcinoma line HT-29 was significantly and comparably suppressed by MT201 and edrecolomab. The fully human nature and the improved ADCC of MT201 with human effector cells will make MT201 a promising candidate for the clinical development of a novel pan-carcinoma antibody that is superior to edrecolomab.

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Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma

Cited by 591 publications

References 24 publications

EpCAM (CD326) finding its role in cancer

EpCAM (CD326) finding its role in cancer

Recombinant polyclonal antibodies for cancer therapy

In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment

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