A Basic Study for Cancer-Specific Immunotherapy using a Human Natural Antibody and its Anti-idiotypic Antibodies.

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SK-1 is a human monoclonal antibody (HuMAb) secreted by a human-human hybridoma generated by the cell fusion method. During 2-year period from April 1999 to March 2001, we made research in the following matters. 1. We made additional 4 human monoclonal antibodies that recognize tumor related antigens. The further investigation to characterize these antibodies is now underway. 2. We evaluated the safety, toxicity and preliminary efficacy of escalating dosages of purified SK-1 in patients with advanced colon cancer. SK-1 was administered intravenously at 2, 4 or 10 mg three times to three groups of patients with recurrent colon cancer. Slight fever that subsided without medication was noted in one patient. No other severe side effects were noted. The mean rate of serum CEA level increase declined significantly during the eight weeks following the treatment (ref.1, 4). 3. We generated murine antiidiotypic monoclonal antibody (Ab2) and rabbit anti-anti-idiotypic antisera (Ab3) to SK1. Using these antibodies we showed that, in four patients, serum titer of antiidiotypic IgG antibodies to SK-1 (Ab2) continued to increase following the treatment. It was suggested that SK-1 natural antibody may have induced carcinoma-related, antiidiotypic antibody responses (ref.1, 4). 4. We identified the gene encoding the SK1-antigenic peptide. A cDNA expression library constructed in λgt22A using mRNA from the colon cancer cell line was screened (ref.3). 5. Adoptive immunotherapy using in vitro activated CD8-positive cytotoxic T lymphocyte was conducted. We showed that, although difficult, CTL can be induced in vitro using autologous tumor cell as an antigen. Once it is induced successfully, favorable clinical effects were seen by the adoptive transfer of such cell populations (ref.6, 7).