Cancer Antigens
Cancer antigens are molecules produced by cancer cells that are recognized by components of the body’s immune system, and which can act as targets for antibody therapies or cancer vaccines.
Brussels LICR scientists cloned the first human cancer antigen, and have identified a significant number of all known cancer antigens.
One of the obstacles in treating cancer is the fact that
tumor cells appear to be almost identical to normal cells.
Conventional chemotherapeutic drugs are unable to
differentiate between cancer cells and normal cells, and most
of the side-effects caused by these conventional therapies
result from normal cells being destroyed along with the
cancer cells. However the body’s own immune system is able to
specifically distinguish between normal and cancer cells by
recognizing cancer antigens displayed on the tumor cell’s
surface.
The pioneering work of Brussels LICR scientists has paved the
way for the development of therapeutic cancer vaccines and
antibodies that target cancer antigens, and thus harness the
immune system to control the spread of cancer.
Cancer Antigens
Antigens are molecules that can be recognized by antibodies or T cells of the immune system either in the forms of an intact molecule, or as smaller, processed fragments.
Cancer antigens fall into several different categories:
- Differentiation antigen - a molecule expressed by one particular tissue-type, and also by cancer cells derived from that tissue-type. For example, the tyrosinase and Melan-A/MART-1 antigens, discovered by LICR scientists, are expressed in normal skin melanocyte cells, and in most melanomas, but not other cell types in the body.
- Mutation and splice variant antigens - alterations in the DNA sequence of a gene frequently result in differences in the gene’s protein sequence when the mutation alters one or more amino acids in the protein. An alteration in the messenger RNA (mRNA) sequence (transcribed from the DNA sequence) may cause the mRNA to be spliced differently, producing different forms of the protein. For example, the NY-CO-38 antigen discovered by LICR scientists, has four splice variants, each of which has a different tissue expression.
- Overexpressed/amplified antigen - a protein that is overexpressed in a cancer cell compared to a normal cell. For example, LICR investigators have discovered that normal epidermal growth factor receptor (EGFR) can be distinguished by a specific targeted antibody when overexpressed.
- CT antigens - proteins expressed only in normal ‘germline’ tissues (testis, placenta, and embryonic and fetal ovary) and in cancer cells. Because germline cells do not express major histocompatibility complex (MHC) molecules, the cells are unable to present antigens on their surface, thus a cancer therapy would not target these normal cells. The NY-ESO-1 antigen, discovered by LICR is a CT antigen; it is expressed in testis, in a variety of tumors such as melanoma, breast, ovary, prostate, bladder, sarcoma, and lung.
- Viral antigens – viral proteins are expressed in infected human cells and these viral proteins, or the peptide fragments resulting from the processing of the proteins, are presented to, and recognized by, the immune system. LICR investigators have identified, and are characterizing antigens that are generated when humans are infected with certain types of human endogenous retroviruses (HERVs), which are though to be etiological agents for several cancers.