Human Monoclonal antibodies - A dual advantaged weapon to tackle cancer and viruses

Human monoclonal antibodies (mAbs) are powerful tools as pharmaceutical agents to tackle cancer and infectious diseases. Antibodies (Abs) are present in blood at the concentration of 10 mg/ml and play a vital role in humoral immunity. Many therapeutic Abs have been reported since early 1980s. Human mAb technology was not available at that time and only the hybridoma technology for making mouse mAbs had been well established. In order to avoid various potential problems associated with use of mouse proteins, two different technologies to make human/mouse chimeric Ab as well as humanized Ab were developed crossing the various hurdles for almost twenty years and mAb based drugs such as rituximab, anti-CD20 Ab, and trastuzumab, anti-HER2 Ab, have been approved by the US Food and Drug Administration (FDA) for treatment of non-Hodgkin's lymphoma and breast cancer in 1997 and 1998, respectively. These drugs are well recognized and accepted by clinicians for treatment of patients. The clinical outcome of the treatment with mAb has strongly encouraged the researchers to develop much more refined mAbs. In addition to chimeric Ab and humanized Ab, now human mAbs can be produced by two technologies. The first is transgenic mice that produce human Abs and the second is human Ab libraries using phage-display system. Until now, several hundreds of mAbs against several tens of antigens (Ags) have been developed and subjected to clinical examinations. While many Abs have been approved as therapeutic agents against hematological malignancies, the successful mAbs against solid tumors are still limited. However, many researchers have suggested that developing potential mAbs agents should be possible and incurable cancers may become curable within another decade. Though it is hard to say explicitly that this prediction is correct, a passion for this development should be worth supporting to lead to a successful outcome which will lead to patient benefits. Our institute has been working on newer technologies for developing human mAbs. For the comprehensive isolation of mAbs, we have developed a method known as ICOS (isolation of antigen–antibody complexes through organic solvent) method (1), in which phage particles of an antibody (Ab) library are mixed with living cells which leads to formation of antigen (Ag)–Ab complexes on the cell surface. The mixture is then overlaid on organic solution and phage bound to cells are recovered from the precipitate after centrifugation [1]. Further, for the rapid identification of Antigens (Ags) recognized by the several mAbs, we have developed the GFC [grouping of clones by flow cytometry (FCM)] method and the SITE (simultaneous identification of clones through three dimensional ELISA) method [2]. These methods helped us to identify 24 distinct tumour associated antigens (TAAs) that are associated with several carcinomas and we were able to isolate 432 human mAbs that specifically bound to one of the 24 TAAs [2], making these mAbs potential therapeutic agents against a variety of cancers. To understand the way forward from our perspectives, a clear knowledge on the following are indispensable Differences between human Abs and the other Abs such as mouse, chimeric and humanized Abs. Differences between Abs and small molecules. Differences between Abs and vaccination. How to materialize best agents using human mAbs. References Akahori Y, Kurosawa G, Sumitomo M, Morita M, Muramatsu C, Eguchi K, Tanaka M, Suzuki K, Sugiura M, Iba Y, Sugioka A, Kurosawa Y. Isolation of antigen/antibody complexes through organic solvent (ICOS) method. Biochem Biophys Res Commun. 2009;378(4):832-5. Kurosawa G, Sumitomo M, Akahori Y, Matsuda K, Muramatsu C, Takasaki A, Iba Y, Eguchi K, Tanaka M, Suzuki K, Morita M, Sato N, Sugiura M, Sugioka A, Hayashi N, Kurosawa Y. Methods for comprehensive identification of membrane proteins recognized by a large number of monoclonal antibodies. J Immunol Methods. 2009;351(1-2):1-12