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The Use of Tolerance to Reduce the Complexity of Reactions to Antigen Mixtures¹

Department of Medical Genetics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

A brief introductory account of the phenomenon of immunologic tolerance is presented as a basis for consideration of its possible application in experimental and clinical oncology.

Some of the various attempts which have been made to produce antibodies to tumor-specific determinants in heterologous hosts, previously treated to render them tolerant of the antigens of corresponding normal tissues, are critically reviewed. It is concluded that although the tolerance method of reducing the complexity of a host's reactions to antigen mixtures is theoretically sound and merits serious attention, it may sometimes fail to detect tumor-specific antigens. This may be due to the fact that the degree of specificity of tolerance is to some extent dependent upon the nature of the antigens concerned.

So far no study based upon the tolerance method has established unequivocally the existence of a tumor-specific antigen. The approach is certainly worth further investigation, but before more effort is expended upon analysis of the complex material afforded by human tumors, critical studies should be carried out upon murine tumors which are known to possess specific antigens, in order to establish the validity and practicability of the method.

¹ The work of the authors in the field of immunologic tolerance has been supported by Grant AI 07001 of the USPHS.