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Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclonal antibody was genetically expressed on human K562 leukemia cells to provide a ligand for T-cell receptor. CD86 and 4-1BBL,which are ligands of co-stimulating receptors of CD28 and 4-1BB,respectively,were also expressed on K562 cells. Then we accomplished the artificial antigen-presenting cells by coupling K32/CD86/4-1BBL cell with OKT3 monoclonal antibody against CD3,named K32/CD86/4-1BBL/OKT3 cells. These artificial modified cells had the abilities of inducing CD8+ T cell activation,promoting CD8+ T cell proliferation,division,and long-term growth,inhibiting CD8+ T cell apoptosis,and enhancing CD8+ T cell secretion of IFN-γ and perforin. Furthermore,antigen-specific cytotoxic T lymphocytes could be retained in the culture stimulated with K32/CD86/4-1BBL/OKT3 cells at least within 28 days. This approach was robust,simple,reproducible and economical for expansion and activation of CD8+ T cells and may have important therapeutic implications for adoptive immunotherapy.
Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclonal antibody was genetically expressed on human K562 leukemia cells to provide a ligand for T- cell receptors. CD86 and 4-1BBL, which are ligands of co-stimulating receptors of CD28 and 4-1BB, respectively, were also expressed on K562 cells. Then we accomplished the artificial antigen-presenting cells by coupling K32 / CD86 / 4- 1BBL cell with OKT3 monoclonal antibody against CD3, named K32 / CD86 / 4-1BBL / OKT3 cells. These artificial modified cells had the abilities of inducing CD8 + T cell activation, promoting CD8 + T cell proliferation, division, and long-term growth, inhibiting CD8 + T cell apoptosis, and enhancing CD8 + T cell secretion of IFN-γ and perforin. Furthermore, antigen-specific cytotoxic T lymphocytes could be retained in the culture stimulated with K32 / CD86 / 4-1BBL / OKT3 cells at l This approach was robust, simple, reproducible and economical for expansion and activation of CD8 + T cells and may have important therapeutic implications for adoptive immunotherapy.