Carcinoembryonic antigen (CEA) in clinical medicine.Historical perspectives, pitfalls and projections

Abstract

Carcinoembryonic antigen (CEA) was first detected by the immunization of rabbits with human colon cancer extract. The techniques of antiserum absorption and immunologic tolerance were employed in an attempt to render the resulting antisera tumor-specific. Using the procedures of precipitation and precipitin-inhibition in gel media, hemagglutination, passive cutaneous anaphylaxis and immunofluorescence, CEA was identified exclusively in all cancers of gastrointestinal origin and fetal digestive organs in the first two trimesters of gestation. The subsequent development of radioimmunoassays for CEA has raised the question of the presence of this material, in very low concentrations, in other normal and diseased (cancerous and noncancerous) tissue, but the problem of cross-reactivity within a family of closely related, but nonidentical, molecules remains to be resolved. CEA was initially purified by a sequence of steps involving extraction in perchloric acid, sieve chromatography, and preparative block electrophoresis. The molecule was characterized as a relatively heterogeneous acid glycoprotein with a molecular weight of approximately 200,000 and its carbohydrate (one-half to two-thirds of the molecule) and protein composition were determined. CEA was localized to the glycocalyx of the colon cancer cell and it was found that the CEA could be released from this site into the circulation of the cancer patient, where it could then be detected by means of radioimmunoassay. The clinical implications of this observation, as they have evolved over the past eight years, form the basis of the papers that constitute this supplement.

Immunization with Mimotopes Prevents Growth of Carcinoembryonic Antigen–Positive Tumors in BALB/c Mice

“…The sequence DRGGLWKTP of linear mimotope clone COL2 was selected for synthetic production of the octameric multiple antigenic mimotope (MAM); ((DRGGLWKTP) 4 -KKGGC) 2 -dithioacetylhexandiamin. The correct fold of the MAM was controlled via Col-1 binding analysis in ELISA.…”

“…CEA was identified for the first time in 1965 in colorectal cancer (4,5) and has since been found in 80% to 90% of all colorectal cancers as well as in up to 50% of all breast cancers, in non -small-cell lung cancers, in esophageal, pancreatic, and gastric malignancies, as well as in malignant tumors of the thyroid and female reproductive tract (6). Levels of CEA are up to 100 times higher in tissue samples derived from malignant tumors as compared with healthy tissues (7).…”

“…The linear peptide mimotope DRGGLWKTP was selected for synthetic production of the octameric peptide (DRGGLWKTP-GG) 4 -(KKGGC) 2 -dithioacetylhexandiamin (piChem) as a so-called multiple antigenic peptide (MAP; ref. 21), which was further designated multiple antigenic mimotope (MAM).…”

“…Slides were incubated with the cells for 20 min, washed twice with PBS, and fixed with 4% paraformaldehyde for 30 min. Thereafter, slides were incubated with 50 mmol/L NH 4 Cl in PBS to quench followed by washing twice with PBS. Cells were incubated with pooled preimmune and seventh mouse immune serum.…”

A personalized view on cancer immunotherapy

“…These studies together with many others in the 1960s, showing the rejection of transplantable tumors in syngeneic mice, reinstated the idea of 'tumor-specific materials', at that time referred to as 'tumor-specific transplantation antigens' [21,22]. In this regard, it is important to mention that the first evidence for the existence of such antigens was delivered by Gold and colleagues who demonstrated humoral responses to an antigen specific for colonic cancer, in particular for the carcinoembryonic antigen (CEA) [23,24]. The existence of antigens, which can elicit specific humoral immune responses and are expressed by tumor cells was confirmed in the late 1970s by Steven Rosenberg and colleagues [25].…”