Tumor Vaccines and Active Specific Immunotherapy ASI

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All forms of vaccination rely on the immune system's active cooperation and support in order to provoke a targeted immune response. This is true also for tumor vaccination, which is therefore referred to as active specific immunotherapy (ASI).

The thesis favored initially, namely, that the immune system distinguishes only between "self"

and "nonself," is no longer valid today (13). Obviously, the immune system recognizes tumors and develops immune responses, although these are often inefficient (48). The recognized antigens are often classic autoantigens, which therefore also occur on normal cells of the body.

Table 19.1 provides a list of representative human tumor antigens. These include, for example, oncofetal antigens and cancer-testis antigens (CTA), which are expressed on embryonic cells or germ cells; they are suppressed in differentiated body cells but may be re-expressed in tumor cells. In addition, tumor antigens include differentiation antigens, viral antigens, and also peptide sequences derived from proteins coded for by mutated or overexpressed genes.

If a tumor cell is supposed to induce a T-cell-me-diated immune reaction, a professional antigen-presenting cell (e. g., a dendritic cell) must phagocytose tumor proteins and, subsequently, present peptide fragments of the tumor antigens on its surface together with genetically determined major histocompatibility complex (MHC) molecules (55). The complex of MHC molecule and tumor peptide is then recognized by cytotoxic (CD8+) or helper (CD4+) T lymphocytes. T-cell activation can only occur when, in addition to antigen recognition, activation signals are mediated to the T cells. This activation includes their proliferation and maturation into effector cells, which are either cytotoxic or release cytokines, such as IFN-y. Cytotoxic T cells can recognize and directly destroy the tumor cell, once the same MHC-tumor-peptide complex has been identified on the malignant cell. This complex sequence of events must be taken into account when developing a successful tumor vaccine.

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