IMMUNOMODULATORY ACTIVITY OF MONOCLONAL ANTIIDIOTYPIC ANTIBODY TO ANTI-COLORECTAL CARCINOMA ANTIBODY-CO17-1A IN ANIMALS AND PATIENTS

Monoclonal anti-idiotypic antibody (Ab2) VF2 was derived from rats immunized with anti-colorectal carcinoma (anti-CRC) monoclonal antibody (Abl) CO17-1A. In rabbits the Ab2 induced anti anti-idiotypic antibodies (Ab3) that shared idiotopes with the Abl, bound to the same epitope on CRC cells as Ab1, and bound to the isolated CO17-1A antigen. Monoclonal Ab2 VF2 was superior to the previously described polyclonal goat Ab2 against Abl CO17-1A in its capacity to elicit humoral immunity in animals. Ab2 VF2 also induced a specific delayed-type hypersensitivity (DTH) response to challenge with irradiated CO17-1A antigen-positive human CRC cells in mice. Of nine CRC patients immunized with aluminum hydroxide-precipitated Ab2 VF2, six developed antibodies that bound to Ab2, but only three patients developed Ab3 that bound to idiotypic determinants on Ab2. However, the Ab3 did not bind to CO17-1A antigen-positive CRC cells. In contrast, in a previously described trial with polyclonal goat Ab2 to Ab1 C017-1A, most of the patients developed anti-CRC antibodies. Four of the nine patients immunized with Ab2 VF2 developed DTH responses to intradermal challenge with the Ab2, and in one patient DTH was both Ab2- and antigen-specific. Peripheral blood mononuclear cells of the four DTH-reactive patients did not proliferate in response to in vitro stimulation with either Ab2 or antigen. These studies demonstrate that the immunomodulatory activity of monoclonal Ab2 VF2 in animals is only in part predictive of its activity in patients.