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).
KeywordsMajor Histocompatibility Complex Molecule Chimeric Receptor Complete DMEM Packaging Cell Line Nylon Wool
- 1.Refisto, N. P., Kawakami, Y., Marincola, F., Shamamiau, P., Taggarse, A., Esquivel, F., et al. (1993) Molecular mechanisms used by tumors to escape immune recognition: immunogene therapy and the cell biology of major histocompatibility complex class I. J. Immunother. 14, 182–190.CrossRefGoogle Scholar
- 6.Grimm, E. A., Muzumber, A., Zhang, H. Z., and Rosenberg, S. A. (1982) Lymphokine activated killer cell phenomenon. Lysis of natural killer resistant fresh solid tumor cells by interleukin 2 activated autologous human periferal blood lymphocytes. J. Exp. Med. 155, 1823–1841.CrossRefPubMedGoogle Scholar
- 14.Eshar, Z., Waks, T., Gross, G., and Schindler, D. J. (1993) Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the γ or ζ subunits of the immunoglobulin and T cell receptors. Proc. Natl. Acad. Sci. USA 90, 720–724.CrossRefGoogle Scholar