Molecular cloning and characterization of a tumor rejection antigen from rat histiocytoma, AK-5.

We have cloned and sequenced a tumor rejection antigen from a highly immunogenic rat histiocytoma, AK-5. Recombinant antigen induced an antibody response in syngeneic hosts, and the immunized animals showed significant resistance to AK-5 tumor challenge, where growth of the tumor was retarded. Autologous anti-AK-5 antibody, as well as the specific monoclonal antibodies raised against whole AK-5 cells, recognized the recombinant protein. Similarly, recombinant antigen was able to neutralize antitumor antibody in a complement-mediated lysis assay. Antibodies raised against the fusion protein recognized a 60-kDa protein from AK-5 cell extracts. A cDNA sequence analysis revealed significant homology with mouse thymus (81%), lymph node (83%), and human brain (71%) cDNAs; however, the function of these genes is not known. These observations suggest the recombinant protein to be a strong candidate for the tumor rejection antigen that is involved in the spontaneous regression of the AK-5 tumor in syngeneic hosts.