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Tumor-specific Transplantation Antigens: G. H. A. Clowes Memorial Lecture¹

Institute for Tumor Biology, Karolinska Institutet, Stockholm 60, Sweden

Tumor-specific transplantation antigens capable of inducing rejection responses of variable strength in genetically compatible (syngeneic) hosts, have been demonstrated in most experimental tumors studied by sensitive assay systems with graded challenge inoculum doses. The reactions are particularly clear-cut in tumors induced by chemical carcinogens and oncogenic viruses, but they could also be demonstrated in a number of "spontaneous" tumors of unknown origin. Antigenic cross-reactivity is the rule for tumors induced by a given virus, whereas chemically induced neoplasms tend to show individually distinct antigenic specificity. This opens new avenues of approach for studies on the phenotype of the neoplastic cell. Provided due regard is given to the passenger virus problem, the demonstration of antigenic cross-reactivity in unknown systems may give new clues with regard to possible etiologic relationships.

The existence of tumor-specific transplantation antigens raises the paradoxical question of how antigenic tumor cells can grow out in spite of host responses. Neonatal thymectomy increases the incidence of certain chemically and virally induced tumors, indicating that immunologic surveillance normally eliminates potentially neoplastic cells in a fraction of the cases. Its failure in others may be related to the immune status of the primary autochthonous host. This is quite different for different systems; documented situations include full and apparently specific tolerance (demonstrated for certain vertically transmitted oncogenic RNA viruses in their natural hosts, particularly some murine leukemia agents and the mammary tumor agent); nonspecific immunodepression (shown for certain chemical carcinogens), sometimes with a superimposed component of specific antigenic paralysis (indicated for mouse methylcholanthrene-induced sarcomas); nonspecific immunodepression due to aging; and a curious state of inertia characterized by the absence of both tolerance and sensitization (exemplified by most DNA virus-induced tumors or by the Schmidt-Ruppin variant of the Rous agent). This inertia is most liable to be influenced by immunologic reinforcement, although the risk of enhancement must be taken into consideration.

The possible therapeutic significance of tumor-specific immune responses still remains to be clarified, but there is good reason to believe that immune responses may contribute to the inhibition of disseminated tumor cells and thus reduce the risk of recurrence, at least in certain systems.

¹ Presented at the 58th Annual Meeting of the American Association for Cancer Research, April 1967, Chicago, Illinois. The work of the author and his associates was supported by grants from the Swedish Cancer Society, the Medical Research Council, by Grants CA-04747 and CA-03700 from the National Cancer Institute, USPHS, from the Damon Runyon Memorial Fund (DRG-598), the Jane Coffin Childs Memorial Fund for Medical Research, and the Knut and Alice Wallenbergs Foundation.

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