During the decade of the 1970s a great deal of progress was made in elucidating how viruses cause cancer. The RNA tumor viruses were shown to harbor cellular genes, often containing mutations, that overexpressed a protein causing the cancer. Long-latency RNA tumor viruses integrated next to or near a cellular gene that was then overexpressed and contributed to the formation of the tumor. By contrast, the DNA tumor viruses encoded their own genes that had no cellular ortholog, but were essential for the initiation and maintenance of the transformed state and tumorigenesis. These viral genes encoded proteins that were expressed in tumor cells and were seen as foreign by animals harboring these tumors. The animals produced antibodies directed against these viral antigens, and for this reason, these viral proteins were called tumor antigens. Accordingly, the transforming genes contained in the SV40 tumor virus were called the large and small tumor antigens, or T and t antigens.

In 1979, David Lane and Lionel Crawford (Lane and Crawford, 1979) and Daniel Linzer and Arnold Levine (Linzer and Levine, 1979) reported that the SV40 T-antigen was bound to a cellular protein that came to be called p53 and that the concentration of the p53 protein was much higher in SV40 or other transformed cells than in normal cells. In fact, temperature-sensitive mutants of T-antigen were shown to control the levels of the p53 protein in a temperature-sensitive fashion (Linzer et al., 1979), and serum from animals bearing SV40-induced tumors contained antibodies to the p53 protein (Linzer and Levine, 1979). At this same time, Lloyd Old and his colleagues showed that animals immunized with spontaneous transformed and tumorigenic cells also made antibodies to the p53 protein (DeLeo et al., 1979). Based upon these studies, p53 came to be classified as a tumor antigen. These observations were the first clue to the mechanism of how the SV40 tumor antigen might trans-