Stimulation of Tumor-Specific Immunity Using Tumor Cell Plasma Membrane Antigen

Abstract

Plasma membranes isolated from tumor cells retain biologically active class I MHC proteins on their surfaces. CD8+T-cell activation by membrane antigen is much more effective when the small membrane vesicles (<1-μm diameter) are displayed on a surface with dimensions approaching those of a cell (5-μm diameter). Previous work had shown that tumor membrane antigen incorporated onto silica microspheres could augment tumor-specific CTL responsesin vivoand significantly reduce syngeneic tumor growth. Antigen on cell-sized solid supports has been termed large multivalent immunogen (LMI). Methods are described for preparing LMI using either silica or latex microspheres. LMI made using either are activein vivoin reducing tumor growth, suggesting that the nature of the support is not critical as long as it is of the appropriate dimensions and has a surface that allows adsorption of the membrane vesicles. Latex microspheres provide some advantages over the previously described silica microspheres with respect to handling and characterization. The effects of LMI onin vivoCTL activation and tumor growth suggest that this approach may have potential for application to clinical immunotherapy of cancers.