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12 - Monoclonal Antibodies for the Delivery of Cytotoxic Drugs

from PART V - ARMING ANTIBODIES

Published online by Cambridge University Press:  15 December 2009

By
David J. King
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
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Summary

Monoclonal antibodies have become an established class of anticancer therapeutics over the last few years, and yet there remains a need for increasing their efficacy, especially in solid tumor therapy. For example, trastuzumab, a humanized antibody to human epidermal growth factor receptor type 2 (HER2, ErbB-2 or HER2/neu), is an FDA-approved antibody for treatment of metastatic breast cancer. Trastuzumab therapy of metastatic breast cancer patients who express the HER2 antigen and had progressed after chemotherapy resulted in a 15% overall response rate, with 4% complete responses and a 9.1 month median duration of response. In first-line treatment of metastatic breast cancer the overall response rate increased to 26%, and it is only in combination with chemotherapy that higher response rates have been found. For example, a response rate of 50% was observed when trastuzumab was combined with a standard chemotherapy regimen. A wide variety of different combinations of trastuzumab with chemotherapy have now been explored demonstrating the use of the antibody in combination therapy and trastuzumab remains a valuable therapeutic agent. Nevertheless, results such as these have led to increased interest in improving antibody efficacy, and the use of antibodies directly attached to cytotoxic agents is being widely explored as one means of achieving this. Indeed, trastuzumab itself is now being investigated as an antibody-drug conjugate.

Antibody-mediated delivery of both protein toxins and chemotherapeutic agents has been under investigation for quite some time and even predates the era of monoclonal antibodies.

Type
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Information
Recombinant Antibodies for Immunotherapy , pp. 157 - 173
Publisher: Cambridge University Press
Print publication year: 2009

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