Tumor Antigen Proteins Background
A commonality of all neoplasms, or tumors, is that they are composed of cells that have accumulated "genetic changes that allow excessive and unregulated proliferation that is independent of physiological growth-regulatory stimuli" (Robbins Basic Pathology, 8th edition) These genetic changes lead to various alterations in cellular protein expression profiles such that when certain peptides are presented at the surface of the tumor cell by major histocompatibility complex (MHC) molecules, they may be recognized as non-self by the immune system.
Tumor antigens can be broadly classified as tumor-specific antigens (TSAs), which are unique to tumor cells and not produced by normal cells, and tumor-associated antigens (TAAs), which are expressed antigens not found exclusively in tumor cells but expressed differently by cancer and normal cells. TSAs may play a functional role in the transformed phenotype of the tumor cell. For example, gain-of-function mutations of pcatenin, a component of the Wnt signaling pathway, are associated with the development of colorectal cancer. Proteins produced by oncogenic viruses, such as human papilloma virus (HPV) and Epstein-Barr virus, represent other types of TSAs that are potentially immunogenic. A recently developed HPV vaccine containing L1 capsid proteins from oncogenic strains (HPV-16 and HPV-18) was shown to be effective in reducing the incidence of high-grade cervical intraepithelial neoplasia in young women.
TAAs are normal cellular proteins that are abnormally expressed in tumor cells. There are a number of different types of TAAs that are categorized based on the normal characteristics of their expression level and location in the body. TAAs may be normally expressed at low levels or only in certain tissues ("differentiation antigens") but are generally overexpressed in tumor cells. For example, tyrosinase, an enzyme involved in melanin biosynthesis, is normally expressed in melanocytes, but is overexpressed in many cases of melanoma. Tumors may also express proteins that are either expressed by normal tissues but are usually hidden from the immune system, for example, within the testis, or that are expressed only during embryological development. These two classes are referred to as "cancer -testis" and "oncofetal" antigens, respectively. Melanoma antigen-1 (MAGE-1) was the first cancer-testis TAA to be discovered. The gene was cloned from a melanoma patient by identifying the segment of tumor cell DNA that conferred susceptibility to attack by autologous cytotoxic T lymphocytes (CTLs). Carcinoembryonic antigen (CEA) represents an example of an oncofetal antigen. CEA is a cell adhesion molecule that is normally expressed during embryonic development, and to a limited extent within adult colonic mucosa. CEA overexpression occurs in nearly all colorectal cancers, 70% of non-small-cell lung cancers, and approximately 50% of breast cancers.