HUMAN COLORECTAL-CANCER (CRC) ANTIGEN CO17-1A GA733 ENCODED BY ADENOVIRUS INHIBITS GROWTH OF ESTABLISHED CRC CELLS IN MICE/

The human colorectal carcinoma (CRC)-associated Ag CO17-1A/GA733, orig inally defined by mAbs CO17-1A and GA733, has been a useful target in passive immunotherapy of CRC patients with mAb and in active immunothe rapy with anti-idiotypic Abs mimicking the CO17-1A or GA733 epitope. B oth approaches have targeted single epitopes. We investigated the capa city of full-length CO17-1A/GA733 Ag expressing multiple potentially i mmunogenic epitopes and encoded by recombinant adenovirus 5 (Ad5 GA733 -2) to induce humoral, cellular, and/or protective immunity in mice. A d5 GA733-2 induced Ag-specific Abs that reacted predominantly to CO17- 1A- and GA733-unrelated epitopes on the Ag and lysed Ag-positive CRC t argets in conjunction with effector cells. Ad5 GA733-2-immune mice dev eloped Ag-specific, proliferative lymphocytes of Th1 type and cytolyti c lymphocytes. The use of Ad5 GA733-2 to immunize mice bearing establi shed syngeneic CRC cells transfected with the human Ag induced signifi cant and specific tumor regression. Cured mice resisted rechallenge wi th human CO17-1A/GA733 Ag-negative parental CRC cells, suggesting that targeting the human Ag on the murine transfectants induced protective immunity to other Ag expressed by the parental tumor. These results m ay explain the high potency of the recombinant vaccine. Thus, rAd5 GA7 33-2 may have potential as a vaccine for CRC patients.