Artificial antigen-presenting cells plus IL-15 and IL-21 efficiently induce melanoma-specific cytotoxic CD8 super(+) CD28 super(+) T lymphocyte responses

Objective: To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8 super(+)CD28 super(+) cytotoxic T lymphocyte (CTL) responses. Methods: Cell-sized Dynabeads registered M-450 Epoxy beads coated with H-2K super(b):lg-TRP2 sub(180-188) and anti-CD28 antibody were used as artificial antigen-presenting cells (aAPCs) to induce melanoma-specific CD8 super(+)CD28 super(+) CTL responses with the help of IL-21 and IL-15. Dimer staining, proliferation. ELISPOT, and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs. Results: Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specifie CD8 super(+)CD28 super(+) CTLs. Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- gamma under the stimulation of H-2K super(b):Ig-TRP2-aAPCs, IL-15, and IL-21. In addition, cytotoxicity experiments showed that induced CTLs have specific killing activity of target cells. Conclusions: The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8 super(+)CD28 super(+) CTLs against the melanoma. Our study provides evidence for a novel adoptive immunotherapy against tumors.