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Bispecific T Cell Engager for Cancer Therapy

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Bispecific Antibodies

Abstract

Treatment with monoclonal antibodies of the human IgG1 and IgG2 isotypes have become a mainstay in cancer therapy, particularly, in hematological malignancies (Ball and Broome 2010). Engagement of Fcγ receptor-bearing immune effector cells, complement fixation, induction of apoptosis, and neutralization of growth factors are major modes of action of conventional monoclonal antibodies. A limited efficacy of such antibodies in oncology as monotherapy has prompted intense efforts in academia and industry to improve their clinical activity. One approach is defucosylation or the introduction of point mutations in the Fcγ1 domain of antibodies, which significantly improves antibody-dependent cellular cytotoxicity (ADCC) (Kubota et al. 2009). Several new antibodies with improved Fcγ receptor-binding properties are now in early-stage clinical development. Another technology to boost antibody efficacy is coupling of toxic payloads, such as chemotherapeutics or bacterial toxins (Alley et al. 2010). While the US market approval for the anti-CD33/calicheamycin conjugate Mylotarg®, the first marketed drug of this kind, has been retracted in 2010, a novel generation of antibody drug conjugates (ADC) is well advanced in development using new technologies for more stably conjugating payloads. For instance, an anti-CD30 for treatment of Hodgkin’s lymphoma called SGN-35, and an anti-Her-2/neu ADC called T-DM1 for treatment of metastatic breast cancer are in pivotal trials and have shown high response rates in patients exceeding those of the parental unconjugated antibodies.

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Authors and Affiliations

  1. Micromet, Inc., 9201 Corporate Boulevard, Suite 400, Rockville, MD, 20850, USA

    Patrick A. Baeuerle, Gerhard Zugmaier & Dominik Rüttinger

  2. Micromet AG, Staffelseestr. 2, 81477, Munich, Germany

    Patrick A. Baeuerle, Gerhard Zugmaier & Dominik Rüttinger

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  1. Patrick A. Baeuerle
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  2. Gerhard Zugmaier
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Correspondence to Patrick A. Baeuerle .

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  1. Inst. Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, Stuttgart, 70569, Germany

    Roland E. Kontermann

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Baeuerle, P.A., Zugmaier, G., Rüttinger, D. (2011). Bispecific T Cell Engager for Cancer Therapy. In: Kontermann, R. (eds) Bispecific Antibodies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20910-9_15

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