The majority of tumor antigens are not unique to tumor cells but also are present on normal cells. These tumor-associated transplantation antigens may be proteins usually expressed only on fetal cells but not on normal adult cells, or they may be proteins expressed at low levels by normal cells but at much higher levels by tumor cells. The latter category includes growth factors and growth-factor receptors, as well as oncogene-encoded proteins.
Several growth-factor receptors are expressed at significantly increased levels on tumor cells and can serve as tumor-associated antigens. For instance, a variety of tumor cells express the epidermal growth factor (EGF) receptor at levels 100 times greater than that in normal cells. An example of an over-expressed growth factor serving as a tumor-associated antigen is a transferrin growth factor, designated p97, which aids in the transport of iron into cells. Whereas normal cells express less than 8,000 molecules of p97 per cell, melanoma cells express 50,000-500,000 molecules of p97 per cell. The gene that encodes p97 has been cloned, and a recombinant vaccinia virus vaccine has been prepared that carries the cloned gene. When this vaccine was injected into mice, it induced both humoral and cell-mediated immune responses, which protected the mice against live melanoma cells ex pressing the p97 antigen. Results such as this highlight the importance of identifying tumor antigens as potential targets of tumor immunotherapy.
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