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Experimental evidence supporting the postulated analogy between myelin basic protein and a previously described common tumour specific antigen is summarized under antigenic cross-reactivity, subcellular localization, molecular size, basicity and proteolipid nature. A third protein antigen, present in all tissues, also shows strong similarities in all these respects.

Intact cells of various human tumours and tumour cell lines, and acid extracts of various human tumours and normal tissues, each of which react with the lymphocytes of cancer patients as detected by the macrophage electrophoretic mobility (MEM) test, have been subjected to proteolysis. Activity was destroyed by some enzymes, and the apparent molecular size of the active material was reduced by others. An active low-mol.-wt fragment has been partially purified from papain digests of several tumours. Peptides with normal tissue and tumour-characteristic activities have been separated chromatographically from tryptic digests of tumour extracts.

(1) The antigenic activity of basic protein extracts of a variety of human tissues towards sensitized lymphocytes from cancer patients has been studied using the macrophage electrophoretic migration method.(2) Basic protein prepared from human tumour tissue has antigenic properties which differ from basic protein prepared from normal tissues, from hyperplastic tissue and even tumour bearing host tissue.(3) Tumour type antigenic molecules are at least 10(4) times less numerous on normal cells than on tumour cells. If our reasoning is accepted then they are absent from normal cells, and thus restricted in vivo to malignant cells.(4) Hyperplastic tissues (gynaecomastia, etc.) do not contain cancer basic protein.(5) Human chronic lymphatic leukaemic leucocytes possess the same type of cancer antigenic activity as solid tumours. This antigenic activity is not shared by normal lymphocytes.

Freshly excised human embryonic tissue used as antigen to test lymphocytes from a cancer bearing patient gives a "normal tissue" result of about 10% in the macrophage electrophoresis migration (MEM) test. When, however, it is grown in vitro and then used as an antigenic stimulant to cancer lymphocytes, a "cancerlike" result (about 15%) is produced. These new antigenic determinant(s) akin to those associated with cancer basic protein appear rapidly (within 5.5 hours) in vitro. Cultures of "normal" cells are thus antigenically different from the same cells in context in vivo.

Patients with advanced malignant disease show an apparent lesser degree of lymphocyte sensitization to cancer antigen when tested under standard conditions than do early cases. In the serum of cancer patients there is a lymphocyte response depressing factor whose titre rises as the neoplasm becomes more extensive. The low lymphocyte response shown by advanced cancers is not, however, directly referable to this rise in depressive factor, but to removal by the tumour mass of specifically sensitized lymphocytes so that amongst the standard number of cells under routine test an adequate number does not remain to give a full response. Increasing the number of cells under test restores the result to the level found in moderately sized cancers. The "absorptive capacity" of large tumours for circulating sensitized lymphocytes is greater than can be provided by natural immunization produced by the tumour. Active immunization with a tumour antigen can be expected therefore to increase lymphocyte-associated defence against cancer.