Direction of the Recognition Specificity of Cytotoxic T Cells Toward Tumor Cells by Transduced, Chimeric T-Cell Receptor Genes

Cellular transformation does not necessarily require the expression of proteins with neoantigenic properties, and for this reason, immunosurveillance does not register all tumor cells. They frequently express potentially immunogenic components, but are able to escape elimination by immune mechanisms. One explanation for this escape is poor antigen presentation by the tumor cells, resulting in little or no measurable antitumor immunity in immunocompetent hosts. T cells remain naive or even become anergic to the tumor cells. Reasons for the deficient antigen presentation by the tumor cells include the reduced or absent expression of major histocompatibility complex (MHC) molecules and the absence of tumor antigens in the groove of class I or class II MHC molecules as a consequence of defective protein processing. Other reasons are the absence or inadequate levels of expression of adhesion molecules, the absence or inadequate levels of costimulatory molecules or the expression of lymphocyte suppressive cytokines like transforming growth factor (TGF-β) or interleukin 10 (IL-10) by tumor cells (1 -5 ).