Edrecolomab (Monoclonal Antibody 17-1A)

Abstract

Edrecolomab is a mouse-derived monoclonal IgG2a antibody. It recognises the human tumour-associated antigen CO17-1A which is expressed on the cell surface of a wide variety of tumours and normal epithelial tissue. Edrecolomab is thought to destroy tumour cells by activating an array of endogenous cytotoxic mechanisms, including antibody-dependent cell-mediated cytotoxicity and possibly antibody-dependent complement-mediated cytotoxicity. Edrecolomab may induce antitumour activity indirectly by inducing a host anti-idiotypic antibody response. Adjuvant therapy with edrecolomab (500 mg initial dose followed by four 100 mg infusions administered at 4-weekly intervals) significantly improved survival and reduced the tumour recurrence rate in patients with resected Dukes' stage C colorectal cancer and minimal residual disease. Data from several small clinical trials suggest that edrecolomab given as monotherapy or in combination with other antineoplastic agents has limited efficacy in the treatment of advanced colorectal or pancreatic tumours. However, results from a small phase I study in patients with advanced breast cancer were more promising. Edrecolomab was generally well tolerated in clinical trials. In a postmarketing surveillance study, the most common adverse events associated with edrecolomab were flushing/erythema and gastrointestinal symptoms including diarrhoea, abdominal pain and nausea and vomiting. Because edrecolomab is of murine origin, anaphylactic reactions have developed in some patients treated with the drug.

EpCAM Is Overexpressed in Breast Cancer and Is a Potential Target for Breast Cancer Gene Therapy

“…Indeed, the use of the EpCAMspecific monoclonal antibody has been successful in increasing disease-free survival in colon and breast cancer patients with minimal residual disease (15,17). These antibodies contribute to tumor cell destruction by activating an array of endogenous cytotoxic mechanisms, including antibody-dependent complement-mediated cytotoxicity (18,19). In addition to being a target of monoclonal antibodybased immunotherapy, there is evidence that EpCAM expression levels correlate with proliferative activity and contribute to neoplastic transformation (1,3,5,7,10).…”

ING-1, a Monoclonal Antibody Targeting Ep-CAM in Patients with Advanced Adenocarcinomas

“…Clinical trials indicate that it is well tolerated, although it has limited antitumor efficacy (21)(22)(23)(24)(25)(26)(27). Nonetheless, in a randomized study of patients with Dukes' C colorectal cancer (28), edrecolomab decreased tumor-related mortality by 32%.…”

EpCAM- AN OLD CANCER ANTIGEN, TURNED ONCOGENIC RECEPTOR AND ITS TAGETING IMMUNOTHERAPY

“…In 1994, mAb17-1A（later named edrecolomab）was also the first to show clinical efficacy in a human cancer indication in terms of prolonged overall survival 62 . Now, several anti-EpCAM therapeutic antibodies have been developed（edrecolomab, ING-1, 3622W94, adecatumumab 63 . The most prominent example is adecatumumab（MT201, a fully human IgG1 antibody that target oncogenic EpCAM, which was well tolerated by patients with hormone-refractory prostate cancer and in patients with rising prostate specific antigen（PSA）levels after radical prostatectomy 43 .…”