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The serum or plasma of 674 patients was studied by means of a radioimmunoassay that detects on carcinoembryonic antigen (CEA) an antigenic site exposed at low ionic strength. Serum specimens from 11 of 299 patients hospitalized for various illnesses other than neoplastic disease had elevated levels of antigen. Subsequently, two of these patients were found to have previously undetected entodermally derived adenocarcinoma. Elevated levels of CEA were observed in serum specimens from 87 of 101 patients with known colonic adenocarcinoma, 30 of 45 patients with breast carcinoma, 26 of 35 patients with lung carcinoma and 20 of 51 patients with prostatic carcinoma. Since serum from patients with both entodermally and nonentodermally-derived carcinoma had elevated levels of CEA an antigenic site common to several tumors appears to exist on CEA.

An ion sensitive antigenic site on carcinoembryonic antigen which has been previously demonstrated to be present in non-entodermally derived tumors and called Tumor Associated Antigen (TAA), has been demonstrated in perchloric acid extracts of normal lung and colon. This antigenic site in normal colon and lung has been shown to be identical to the antigenic site on carcinoembryonic antigen (CEA) by radioimmunoassay and Ouchterlony analysis. This provides further evidence that a common antigenic site exists on CEA as CEA is found only in entodermally derived tumors and is truly tumor specific. This antigenic site in nonentodermally derived tumors and normal tissues is structurally and chemically similar to CEA and further defines the tumor associated antigenic site (TAA).

Tritiated 3–2′Dimethyl-4-diphenylamine was prepared by catalytic exchange and studies were carried out in Wistar-Furth rats following subcutaneous injection. Blood levels reached their peak in 12 hours and this correlated closely with the peak levels of label in the urine and bile. Ninety per cent of labelled compound was excreted within 5 days, less than 3% of the tritium excreted was in the form of tritiated water. Sixty-five per cent of excreted label appeared in the stools, and 35% in the urine of intact animals. In animals with bile fistula, 85% of the label appeared in the bile and 15% appeared in the urine. This data suggested recirculation of the compound and radioautographs were done at 10 and 20 hours after injection of labelled carcinogen, to see if there was any preferred site of absorption in the G.I. tract. None was found. Radioautographs failed to show any preferred localization of the label in the cells of the G.I. tract, liver, kidney, or bladder.

A method for the preparation of tumor-associated antigen (TAA) is described. We have been able to demonstrate two antigens with common antigenic determinants that are separable by ion-exchange chromatography and electrophoresis. These antigens appear identical by Ouchterlony immuno-diffusion analysis and by Sephadex chromatography. The differences in electrophoretic mobility of these antigens appear related to a sialic acid moiety, although we have demonstrated that the antigenic specificity does not reside in this portion of the molecule. These antigens share at least one common determinant with a low-molecular-weight substance found in perchloric acid extracts of normal lung and colon. This and previous studies would suggest that this antigen is identical to carcinoembryonic antigen (CEA).

The zirconyl phosphate gel assay (Z-gel) was used to assay sera of 265 patients for humoral activity against carcinoembryonic antigen (CEA). Included in the patients tested were 110 with non-metastatic colon carcinoma, 122 with other gastrointestinal, breast and pulmonary neoplasms, 20 pregnant women and 13 healthy volunteers. Twenty-five of the patients were also analyzed with molecular filtration column chromatography. Antibody activity directed against CEA could not be detected with either technique. Possible explanations for these results are discussed.

Halothane and Cyclopropane anesthetics had little or no effect on the immune competence of lymphocytes as measured by their response to PHA. These results again demonstrate the rapid irreversibility of the cellular effects of these anesthetics and suggest that the inhibition of the immune response seen in post operative patients is related to serum factors yet undermined.

Ten patients receiving systemic chemotherapy for metastatic tumors of the G. I. tract and lung are studied with serial determinations of TAA levels during their therapy. The pattern of changes of TAA levels in each patient is correlated with the clinical response of that patient. Significant decreases in TAA levels occurred concomitant with clinical improvement in three patients. Significant, sustained elevations in TAA levels were invariably associated with inexorable deterioration clinically. This occurred in 6 patients. This preliminary study suggests positive correlations may be present which would make serial TAA levels a useful guide to the effectiveness of chemotherapy in solid tumors.