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Nonvirus-associated Antigens in Virus-induced Mouse Mammary Tumors¹

Cancer Research Genetics Laboratory and Department of Bacteriology and Immunology, University of California, Berkeley, California 94720

Common, cross-reacting virus-associated tumor antigens have been demonstrated by many workers in most virus-induced experimental tumor systems, including mammary tumors induced by the mouse mammary tumor virus (MTV). By the use of mice neonatally infected with the MTV and therefore immunologically tolerant of this virus and its associated antigens, other antigens have now been detected in MTV-induced tumors which do not cross-react and which, accordingly, are probably not related directly to the inducing virus.

The immunogenicity of 23 spontaneous mouse mammary carcinomas was tested in MTV-infected C3H hosts. The immunization procedure consisted of subcutaneous implantation of living tumor tissue. The challenge was with suspensions of living tumor cells at the time of removal of the immunizing grafts. Immunity was manifested by rejection of the challenge implants by a high proportion of the presensitized hosts. Of the 23 tumors, 5 were found to induce high resistance to challenge in repeated tests. It is concluded that nonvirusassociated antigens are found in some C3H mammary carcinomas.

Histologic studies showed that presensitization resulted in lymphocytic invasion of challenge implants of tumor tissue.

Immunity to tumor-cell implants was adoptively transferred to C3H recipients with lymphocytes from sensitized C3Hf donors.

Four of the immunogenic tumors were tested for cross-immunization in C3H mice. In one test reciprocal cross-reactivity was found between two tumors. In 3 tests involving the remaining two and one of the former tumors, no cross-reactivity was detected. All 4 tumors cross-reacted in MTV-free C3Hf mice.

These findings, together with other evidence, show that mouse mammary tumors contain a common component which is immunogenic in the MTV-free C3Hf mice but not in the MTV-infected C3H mice. In addition, some tumors contain tumor-specific antigens which are unrelated to the MTV and which make them immunogenic in the MTV-infected C3H mice.

¹ This work was supported by Research Grant E-344 from the American Cancer Society, Inc; Grants CA-04388, CA-05045, and CA-08357 from the National Cancer Institute, NIH, USPHS, and by Cancer Research Funds of the University of California.

Received 4/ 8/68. Accepted 8/26/68.