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 responses in vivo and 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 microsphere's. LMI made using either are active in vivo in 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 on in vivo CTL activation and tumor growth suggest that this approach may have potential for application to clinical immunotherapy of cancers.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health Grant AI31524. E.S. was supported in part by an NCI Oncology Research Faculty Development Award. We thank Paul Champoux for excellent technical assistance.