The Use of Monoclonal Antibody Immunoconjugates in Cancer Therapy

Abstract

The conventional therapeutic approaches to breast cancer, including surgery, radiotherapy and cytotoxic drugs, has led to a certain degree of responsiveness which has not significantly changed in the last 20 years. Because of the high incidence of breast cancer, there is a real need to use additional forms of therapy which could potentially lead to a cure of this disease. In this light, new therapeutic approaches using antibodies (either alone or as immunoconjugates as discussed herein), or antigen (as in vaccination procedures) are receiving close attention. The current status of vaccines for breast cancer is considered elsewhere in this volume, and here we review the use of antibody based therapy. It should be noted that while antibodies are discussed in this chapter as a means of conveying toxic moieties to tumors, other carriers such as serum proteins (eg transferrin), cytokines (eg. IL-2) and other moieties have been used; these have been reviewed elsewhere¹. At this time, there is some pessimism regarding the value of antibody immunoconjugates for the therapy of cancer, and at the outset we would like to dispel this pessimism for the following reasons: a) few, if any trials have progressed beyond Phase I/II and a formal comparison with other modes of therapy has not been done; b) as these are early studies, most of the patients used for therapeutic purposes had very large lesions and it would be most unlikely that complete responses could be obtained (as will be discussed below, it is our belief that immunoconjugates will find a place, and control the treatment of small metastic deposits arising from the treatment of large volume disease); c) the treatment of solid tumors usually has to be curtailed because of the occurrence of human anti-mouse antibody (HAMA) responses, and the maximum tolerated dose of immunoconjugate has rarely been achieved.