Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer

Kiewe, Philipp; Hasmüller, Stephan; Kahlert, S.; Heinrigs, M.; Rack, B; Marmé, Alexander; Korfel, Agnieszka; Thiel, Eckhard; Sommer, H.; Untch, Michael

doi:10.1200/jco.2005.23.16_suppl.2530

Cited by 42 publications

(59 citation statements)

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“…In another approach, a bispecific antibody that targets HER2 as well as CD3 antigen on T cells was developed to recruit T cells to tumor cells. This agent showed promising evidence of activity in its phase I study and further studies are underway to determine its antitumor efficacy (Kiewe et al, 2006). In another approach, the in vitro ADCC activity of trastuzumab appears to be augmented by defucosylation, and the fucosyl-negative version of trastuzumab has been proposed for clinical testing (Suzuki et al, 2007).…”

Section: Mechanism Of Action Of Trastuzumab -Immunological Targetingmentioning

confidence: 99%

Targeting the function of the HER2 oncogene in human cancer therapeutics

2007

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Section: Mechanism Of Action Of Trastuzumab -Immunological Targetingmentioning

confidence: 99%

Targeting the function of the HER2 oncogene in human cancer therapeutics

2007

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“…Two promising bispecific antibodies, anti-HER2 Â anti-CD3 Ertumaxomab (Kiewe et al, 2006) and anti-FcgRI Â anti-HER-2 MDX-H210 (Schwaab et al, 2001;Repp et al, 2003), are currently in clinical trials. The concept of bispecific antibodies will be discussed in detail later.…”

Section: Naked Antibodiesmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

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“…Encouraging first clinical results confirm those observed in in vitro anti-tumour potency studies. Positive indication of clinical benefit in the treatment of metastatic breast cancer came from a phase I dose escalation trial using a HER-2-specific trAb (Kiewe et al, 2006). Moreover, the feasibility of combining trAbs with high-dose chemotherapy for metastatic breast cancer treatment was shown in a pilot study (Stemmler et al, 2005).…”

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confidence: 99%

Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer

Rosenberger¹,

Gires²,

Jäger³

et al. 2007

Br J Cancer

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Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is frequently overexpressed in a variety of carcinomas. This pan-carcinoma antigen has served as the target for a plethora of immunotherapies. Innovative therapeutic approaches include the use of trifunctional antibodies (trAbs) that recruit and activate different types of immune effector cells at the tumour site. The trAb catumaxomab has dual specificity for EpCAM and CD3. In patients with malignant ascites, catumaxomab significantly increased the paracentesis-free interval, corroborating the high efficacy of this therapeutic antibody. Here, we characterised the monoclonal antibody (mAb) HO-3, that is, the EpCAM-binding arm of catumaxomab. Peptide mapping indicated that HO-3 recognises a discontinuous epitope, having three binding sites in the extracellular region of EpCAM. Studies with glycosylation-deficient mutants showed that mAb HO-3 recognised EpCAM independently of its glycosylation status. High-affinity binding was not only detected for mAb HO-3, but also for the monovalent EpCAM-binding arm of catumaxomab with an excellent K D of 5.6 Â 10 À10 M. Furthermore, trAb catumaxomab was at least a 1000-fold more effective in eliciting the eradication of tumour cells by effector peripheral blood mononuclear cells compared with mAb HO-3. These findings suggest the great therapeutic potential of trAbs and clearly speak in favour of EpCAM-directed cancer immunotherapies.

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Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer

Cited by 42 publications

References 0 publications

Targeting the function of the HER2 oncogene in human cancer therapeutics

Targeting the function of the HER2 oncogene in human cancer therapeutics

Novel antibodies as anticancer agents

Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer

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