PRECLINICAL EVALUATION IN NONHUMAN-PRIMATES OF AN ANTIIDIOTYPIC ANTIBODY THAT MIMICS THE CARCINOEMBRYONIC ANTIGEN

We have developed and characterized a murine monoclonal antiidiotype ( Id) antibody (Ab2), designated 3H1 (IgG1-k) that mimics human carcinoe mbryonic antigen (CEA). 3H1 was raised against an anti-CEA monoclonal antibody (mAb) 8019 (Ab1) that recognizes a distinct and specific epit ope of the 180,000 MW CEA. 3H1 induced specific anti-CEA immune respon ses in mice and rabbits. In this preclinical study, cynomolgus monkeys (Macaca fascicularis) were immunized with aluminum hydroxide-precipit ated 3H1 and tested for the induction of anti-CEA antibodies. Monkeys were injected with 2 mg of 3H1, intracutaneously, four times biweekly. All monkeys developed specific anti-anti-Id (Ab3) responses that were capable of inhibiting binding of the immunizing 3H1 (Ab2) to 8019 (Ab 1) and vice versa. Furthermore, immune sera from monkeys contained Ab3 (Ab1') antibody that bound to CEA-positive colon carcinoma cell lines but not to CEA-negative MOLT-4 or melanoma cell lines. Also, the Ab3 reacted with purified CEA and competed with Ab1 (8019) for binding to CEA positive LS174-T cells, suggesting that Ab1 and Ab3 may bind to th e same epitope. In addition, affinity-purified Ab3 from monkey sera im munoprecipitated the same 180,000 MW CEA as Ab1 8019 and showed an ide ntical pattern as the Ab1 on colon carcinoma specimens by immunoperoxi dase staining. The induction of anti-tumor antibodies in monkeys did n ot cause any apparent side effects. These data suggest that internal i mage anti-Id can induce tumor-specific humoral immune responses in non human primates and can serve as potential network antigen for triggeri ng active anti-CEA antibodies in colorectal cancer patients.