Natural antibodies in human sera directed against blood‐group‐related determinants expressed on colon cancer cells

Sera from 136 normal males and 33 members of families at high risk for colon cancer were tested for reactivity with six colon cancer cell lines by the protein A‐mixed hemadsorption assay. Ninety‐one sera had antibodies to colon cancer cell line HT‐29. In 89 cases the antibodies were absorbed by human A and B erythrocytes or sheep erythrocytes. Antibodies in the remaining two sera, which were from sisters in the high‐risk group, were not absorbed by red cells but could be absorbed by tumor cells expressing A or B blood‐group determinants. Their reactivity was inhibited by some soluble blood‐group glycoproteins. One serum (No. 4) was inhibited by A‐active glycoproteins from human saliva and ovarian cyst fluids and from porcine mucosa, as well as by a polysaccharide derived from gastric cancer; it has an anti‐A‐like specificity. The other serum (No. 6) was inhibited by A and B glycoproteins, by a blood group precursor glycoprotein and by the same gastric cancer polysaccharide; it seems to have a wider specificity directed towards both A‐ and B‐like structures. It is not known what caused production of these antibodies but it may be significant that they occurred in members of a family at high risk for developing colon cancer.