ACTIVE IMMUNOTHERAPY TO HUMAN CARCINOMA ASSOCIATED ANTIGENS

主动特异性免疫治疗是一种新的、潜在的无毒方法

Active specific immunotherapy is a new and potentially non toxic approach for cancer therapy. Tumor associated antigens could serve as targets for this type of therapy. Carcinoembryonic antigen (CEA) is a 180,000 dalton oncofetal glycoprotein expressed on most gastrointestinal carcinomas and many other human carcinoma types. CEA is generally considered to be weakly immunogenic in humans; that is, little evidence exists for humoral or cell mediated immunity to CEA in normal or cancer patients. The copresentation of CEA with a strong immunogen would represent a logical approach to inducing anti-CEA responses for tumor immunotherapy. Recent advances in recombinant vaccinia virus technology has provided a powerful method for antigenic copresentation. To this end, a 2.4 bb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and was inserted into a vaccinia virus genome. This recombinant construct was characterized by Southern blotting, restriction endonuclease digestion, polymerase chain re action analysis, and subsequent DNA hybridization. The CEA gene was stably integrated in the vaccinia virus thymidine kinase gene. This recombinant was efficiently replicated upon serial passages in cell culture and in animals. The recombinant virus expressed on the surface of infected cells, a protein product recognized by the MAb COL-1 directed against CEA. Immunization of mice with the recombinant vaccinia virus resulted in a humoral immune response against CEA.Pilot studies demonstrated that the administration of the recombinant vaccinia virus was able to greatly reduce the growth of tumors in mice. This murine colon adenocarcinoma had been transduced with the human CEA gene, expressed human CEA, and grew in syngeneic animals. The use of this new recombinant CEA vaccinia virus may provide a new approach in the specific active immunotherapy of human gastrointestinal cancer and other CEA expressing carcinoma types.