IMMUNOLOGY - Roit A. - Mir 2000

Chapter 20. Tumor Immunology

TUMOR-ASSOCIATED ANTIGENS RECOGNIZED BY ANTIBODIES

Some Antigens are unique to tumors

Numerous studies aimed at identifying tumor-specific antigens have employed either serum from the tumor-bearing animal itself (autologous typing) or sera from animals immunized with tumor tissue (heterologous typing). More recently, investigations have begun using Monoclonal Antibodies derived from autologous or heterologous B Cells. While definitive evidence for true tumor-specific antigens remains sparse, several types of antigens associated with tumors in various ways have been successfully identified.

Sera from Cancer patients reveal widely distributed antigens

When using sera from cancer patients or monoclonal antibodies raised against their tumor cells, researchers typically detect antigens that are broadly expressed On the surface—or, more frequently, in the interior—of both tumor and normal cells. The corresponding antibodies largely belong to the IgM Class and consequently exhibit low affinity. Similar monoclonal antibodies can be generated using immortalized B cells from healthy individuals. These antibodies recognize autoantigens, and their role, if any, in the body's Immune Response to tumors remains unclear.

Tumor Immunology

Tumors may express normal differentiation antigens characteristic of rare normal Cell types

Most tumor cells represent a clone—the progeny of a single cell—and cells of that specific Lineage may be relatively scarce in the body. Consequently, tumor cells express antigens that are normally present only in select types of normal cells. Examples of such antigens include the common acute lymphoblastic leukemia antigen (CALLA, or CD10) (Fig. 20.7) and carcinoembryonic antigens (CEA), which function as differentiation antigens expressed during embryonic development but typically absent (or expressed at extremely low levels) in adult Tissues.

CEAs include α-fetoprotein (AFP), produced by Liver tumor cells, and antigens produced by human colon carcinoma cells and other epithelial tumors.

Fig. 20.7.

1. CALLA is normally expressed only on precursor B cells (lymphoblasts), which account for less than 1% of normal Bone Marrow cells. 2. CALLA expression is significantly upregulated in the most common form of childhood leukemia.

Normal cellular antigens expressed by tumors can be altered through glycosylation

Alterations in the glycosylation of cellular molecules are a hallmark of many tumors. These changes can lead to the expression of novel carbohydrate epitopes, such as the Thomsen-Friedenreich antigen—a disaccharide not typically detected on normal cells. Aberrant Blood Group Antigens can arise in a similar fashion. Furthermore, altered glycosylation can expose protein backbone epitopes that are rarely accessible in normal cells. A prime example is provided by polymorphic epithelial mucins produced by many normal epithelial cells. These are high-molecular-weight Glycoproteins in which a repeating core peptide carries carbohydrate side chains. In epithelial tumors, a novel protein epitope is revealed within this core Structure.