ABSTRACT
Cancer has been the ϐirst or second main cause of death of humans in developed countries in the past few decades. Great many efforts have been undertaken for the control of cancer; toward this goal, chemotherapy plays an important role. However, the decisive effect against cancer was limited, although so many anticancer drugs have been developed. One of the major problems that limit successful cancer chemotherapy is the lack of selectivity to tumors; instead, these agents also cause damage to normal tissues and organs, which induces adverse effects to certain organs, leading to doselimiting toxicity. To overcome these obstacles, since the 1970s, many strategies have been challenged to make anticancer drugs more selective to tumors. One method to achieve this goal is to utilize antibodies directed to speciϐic tumor epitopes of certain proteins or
enzymes, such as trastuzumab, rituximab, radiolabeled antibodies ibritumomab, tiuxetan (Zevalin), tositumomab (Bexxar), and bevacizumab (Avastin) [1]. These drugs exhibit promising anticancer effects with lesser toxicity in mice tumor models compared to conventional anticancer drugs. However, it is now realized that the success rate or response rate of these molecular target drugs is no better than 10% in clinical settings. Although some success is seen in imatinib (Gleevec), most of the advanced molecular target drugs are disappointing. Factors causing therapeutic failure are mostly related to the heterogeneity of tumor antigens and, secondly, the emergence of resistant subclones. Recent progress in cancer genomics showed that excessively high incidence of mutation occurred in cancer genomes [2-5]. In addition, there may be the likelihood that the tumor-associated antigens are shed into the blood circulation. As a result, the antibody might encounter the tumor antigens before it reaches the target tumor, and hence the therapeutic efϐicacy will be reduced, if not abolished.
