A series of 14 monoclonal anti-carcinoembryonic antigen (CEA, Mr 180,000) antibodies (MAbs) that show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues were used to construct a serological map of the CEA molecule. The MAbs were generated using extracts of colon carcinomas as immunogen and are thus given a COL designation. None of the 14 COL-MAbs tested were reactive with purified non-specific cross-reacting antigen (NCA, Mr 55,000) from normal lung, although some showed reactivity to human granulocytes. All the COL-MAbs tested were reactive with normal fecal antigen-2 (NFA-2, Mr 170,000); however, many of the COL-MAbs demonstrated a higher affinity constant to CEA than to NFA-2. Cross-competition radioimmunoassays classified the 14 COL-MAbs into 5 groups. The chemical nature of the COL-binding domains was tested using chemically or enzymatically treated CEA; all reacted with periodate-treated CEA and deglycosylated CEA, indicating that the COL-reactive epitopes appear to be of a proteinaceous nature. Heat treatment, reduction, alkylation, pepsin digestion or pronase treatment of CEA, however, gave differential results with respect to COL binding. Antibody titration experiments were carried out to define differential reactivities to colorectal carcinoma versus NCA-containing granulocyte extracts; these results were compared with results obtained using several anti-CEA MAbs that have been used in clinical trials. Granulocyte binding and biochemical studies showed that the COL MAbs may distinguish as many as 7 to 10 CEA epitopes.

The ongoing development of monoclonal antibody technology may eventually lead to the selective targeting of human carcinoma lesions by MAbs conjugated with a variety of cytotoxic agents (i.e., radionuclides, drugs, etc.). The antigen phenotype of the carcinoma cell will play an important role in the efficacy of the MAbs. Clearly, the human tumor antigens that are expressed on all carcinoma cells, and with a high antigen density, should provide the optimal target for the MAbs. More often than not, however, the human tumor antigens whose expression is highly selective for human tumor cells will also exhibit a certain degree of heterogeneity. Therefore, the ability of interferon to augment the level of expression of human tumor antigens such as TAG-72 and CEA, may play an important role in an adjuvant setting for immunoscintigraphy and/or immunotherapy. More recent observations have demonstrated that interferon treatment can also enhance the amount of TAG-72 and CEA secreted by the tumor cell. The ability of interferon to enhance the shedding of both TAG-72 and CEA could be of particular importance since recent reports suggest that their presence in the sera of patients diagnosed with gastrointestinal adenocarcinoma may be complementary and that the ability to increase either marker may facilitate earlier diagnosis of recurrent disease. It is conceivable that in subsequent years effective approaches to monitoring and/or treating malignancies may include a new combination of biological/immunological therapy.

The role of prostaglandins in the regulation of adrenocortical function remains unresolved. Flack and Ramwel/ (1972) demonstrated an increase in steroid production by rat adrenal tissue after addition of prostagIandin EI (PGE I ) or E2 (PGE 2 ) in vitro. However, results of so me studies (Peng, Six and Munson 1970, Blair-West, Coghlan, Denton, Funder, Scoggins andWright 1971) indicate that prostaglandins do not directIy affect adrenal secretion. Data concerning the relationship between ACTH action and prostaglandins are also in apparent conflict. Dazord, Morera, Bertrand and Saez (1974) demonstrated