Purpose To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of gastrointestinal cancers. Methods For the 2006 update, an update committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of Medline and the Cochrane Collaboration Library were performed. The Update Committee’s literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies.

https://ascopubs.org/doi/pdf/10.1200/JCO.2006.08.2644

ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer

Publisher Summary Aberrant glycosylation is the most common phenomenon associated with oncogenic transformation expressed in cell membranes of animal and human cancer cells. Such aberrant structures at the surface membranes may well be effective targets in prevention, diagnosis, and treatment of human cancer. Many of the aberrant glycosylation products can be recognized by specific MAbs as tumor-associated carbohydrate antigens. Many of these antigens have been identified as carbohydrates, thus there is increasing evidence that essentially all human cancers are characterized by aberrant glycosylation. Aberrant glycosylation as such may be the basis of inappropriate cell/cell and cell/matrix interactions that may be reflected in the abnormal cell social behavior of tumor cells, such as uncontrolled cell growth, invasiveness, and metastatic potential. Whatever the genetic or epigenetic basis of expression of aberrant glycosylation is, the phenomenon is of crucial importance in understanding the antisocial behavior of tumor cells as well as in practical applications in diagnosis and treatment of human cancer.

Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens

Immune escape is a crucial feature of cancer progression about which little is known. Elevation of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) in tumor cells can facilitate immune escape. Not known is how IDO becomes elevated or whether IDO inhibitors will be useful for cancer treatment. Here we show that IDO is under genetic control of Bin1, which is attenuated in many human malignancies. Mouse knockout studies indicate that Bin1 loss elevates the STAT1- and NF-kappaB-dependent expression of IDO, driving escape of oncogenically transformed cells from T cell-dependent antitumor immunity. In MMTV-Neu mice, an established breast cancer model, we show that small-molecule inhibitors of IDO cooperate with cytotoxic agents to elicit regression of established tumors refractory to single-agent therapy. Our findings suggest that Bin1 loss promotes immune escape in cancer by deregulating IDO and that IDO inhibitors may improve responses to cancer chemotherapy.

Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy.

Immunoblotting and dot immunobinding--current status and outlook.

A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II.

Hybridoma cells which secrete colorectal carcinoma-specific antibodies have been produced and used to study the antigenic structure of these tumor cells. Nineteen antibodies have been studied in detail, and 15 of these are colorectal carcinoma specific. Only two antibodies reactive with carcinoembryonic antigen (CEA) have been discovered and five other antibodies that react with distinct epitopes on the cell surface have been defined. Several antigens with distinct molecular characteristics have been shown to exist by use of hybridoma antibodies. Six hybridoma antibodies have been shown to mediate antibody-dependent cell-mediated cytotoxicity (ADCC).

Colorectal carcinoma antigens detected by hybridoma antibodies

The antigen of a monoclonal antibody that is specific for cells of human carcinoma of the colon is a monosialoganglioside as determined by the direct binding of antibody to thin-layer chromatograms of total lipid extracts of tissues. Binding of antibody to chromatograms is detected by autoradiography after the application of iodine-125-labeled F(ab')2 of rabbit immunoglobulin G antibodies to mouse immunoglobulins.

A monosialoganglioside is a monoclonal antibody-defined antigen of colon carcinoma.

We have constructed cell-specific cytotoxic agens by covalently coupling the A chain from diphtheria toxin or ricin toxin to monoclonal antibody directed against a colorectal carcinoma tumor-associated antigen. Antibody 1083-17-1A was modified by attachment of 3-(2-pyridyldithio)propionyl or cystaminyl groups and then treated with reduced A chain to give disulfide-linked conjugates that retained the original binding specificity of the antibody moiety. the conjugates showed cytotoxic activity for colorectal carcinoma cells in culture, but were not toxic in the same concentration range for a variety of cell lines that lacked the antigen. Under defined conditions virtually 100% of antigen-bearing cultured cells were killed, whereas cells that lacked the antigen were not affected. Conjugates containing toxin A chains coupled to monoclonal antibodies may be useful in studying functions of various cell surface components and, possibly, as tumor-specific therapeutic agents.

https://www.pnas.org/content/pnas/77/8/4539.full.pdf

Antibody-directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells

This report describes the structures of three distinct human melanoma surface antigens detected by monoclonal anti-melanoma antibodies. One antigen, expressed on all melanoma cells and on certain astrocytoma cells but not on any other kind of normal or tumor cell tested, has been shown to consist of our associated polypeptide chains. A second antigen expressed on many but not all melanomas has been identified as the antigenic product of the HLA-D locus, the DR antigen. A third protein antigen is not found on any normal cell tested but occurs on some, but not all, tumors of various origins.

Biochemical characterization of human melanoma cell surfaces: dissection with monoclonal antibodies.

Monoclonal antibodies were used to define four distinct antigens present on the surfaces of human lung tumors. Immunoprecipitation of the four antigens by monoclonal antibodies and sodium dodecyl sulfate:polyacrylamide gel electrophoresis reveals that they have distinct complex structures. Different patterns of expression of these antigens on cells of other than lung tumor origin were detected by the same panel of monoclonal antibodies.

https://cancerres.aacrjournals.org/content/canres/42/1/150.full.pdf

Kenneth F. Mitchell

Papers

Colorectal carcinoma antigens detected by hybridoma antibodies

A monosialoganglioside is a monoclonal antibody-defined antigen of colon carcinoma.

Antibody-directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells

Biochemical characterization of human melanoma cell surfaces: dissection with monoclonal antibodies.

Monoclonal antibody-defined human lung cell surface protein antigens.