Detection of Antigens in Sera of Patients with Neoplastic Disease by Schultz-Dale Test

the bonds between carbohydrates and proteins (Meyer and Rapport, 1951), while heat to 100' C. denatures the proteins. This probably explains why treatment with heat and alkalis does not destroy their ability to immunize guineapigs or to release the Schultz-Dale reaction. The fact that such activity persists after ether extraction tends to refute the lipid nature of cancer antigens. The slight improvement in antigenicity resulting from ether extraction is again consistent with a polysaccharide nature, since polysaccharides have a great affinity for lipids. Moreover, the polysaccharide nature of the antigen explains the greater activity of the supernatant, as compared with the sediment, in releasing the Schultz-Dale reaction. The less soluble and less active components are probably the result of gradual drying of tissues. This, according to Whistler and Smart (1953), occurs when highly hydrated polysaccharide material is air-dried. The gradual removal of water molecules allows neighbouring polysaccharide molecules to come together and establish strong bonds which later restrain the separation of molecules. This reduction in surface area and in the number of active available sites on the polysaccharide molecules could be regarded as a form of polymerization, and would account for the in vitro reduction of antigenic activity-that is, its capacity to release the reaction in the Schultz-Dale bath-of the sediment as compared with the supernatant. These studies also raise the question of the relatively " normal " nature of the healthy colon tissue obtained from the patient Handy, who did have a carcinoma of the colon. Is pathologically " normal ' tissue necessarily immunologically "normal"s? Is the better control tissue to use in this case " normal " colon from the same patient or from a young healthy accident case ? The above findings indicate the presence of the specific carcinoma polysaccharide-like antigens in these so-called "normal" portions from the carcinoma patients, although to a less extent than in the neighbouring neoplastic tissue. They also indicate that this soluble polysaccharide-like antigen is present not only in the cancerous tissue but also in the blood and other tissues, even those that appear pathologically "normal." This was the reason for the use in later studies of homologous tissues from a healthy individual rather than from the cancer patient himself. The polysaccharide nature of cancer antigens could easily explain why mast cells and tissue polysaccharides are the predominating elements in the development and growth of connective-tissue tumours as shown by Sylven (1945), Holmgren and Wohlfart (1947), and Gersh and Catchpole (1949). It could also explain the greatly increased amounts of polysaccharides always found in the serum of cancer patients. Furthermore, it throws new light on the finding of high levels of hyaluronidase inhibitors in the blood of patients with disseminated cancer by Kiriluk et al. (1950) and with certain leukaemias and lymphomas by Hentstell and Freedman (1951). The association of polysaccharides with polypeptides is well known. Morgan (1941) and Partridge and Morgan (1942), for example, were able to make artificial complexes using "polypeptide-like" substances isolated from Shiga, and carbohydrates such as group A substance from commercial pepsin. It was found that these " polypeptide-like " substances appear to have a special power to form antigenic complexes with polysaccharides. It is our belief that the activity of the polypeptide found by Burrows and Neill (1958) in the serum of cancer patients is due to an associated polysaccharide antigen. The finding by Winzler (1953), referred to by Burrows and'Neill, of an increase in polypeptides in the serum in carcinoma, and specifically of mucopolypeptides, strengthens this possibility. Polysaccharides are less complex to study immunochemically than are proteins. This finding, therefore, of the polysaccharide nature of cancer antigens should give us a little more reason for optimism in our attempts to understand the cancer problem and a greater hope of its solution. These results are preliminary in nature, and work along these lines is being continued at the Muhlenberg Hospital. Further evidence for the polysaccharide nature of cancer antigens, using another immunological technique, will be published elsewhere.