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

Objective: To develop a novel artificial antigen presenting system for efficiently inducing melanoma specific CD8(+)CD28(+) cytotoxic T lymphocyte (CTL) responses. Methods: Cell-sized Dynabeads (R) M-450 Epoxy beads coated with H-2K(b):Ig-TRP2(180-188), and anti-CD28 antibody were used as artificial antigen-presenting cells (aAPCs) to induce melanoma-specific CD8(+)CD28(+) CTL responses with the help of 1L-21 and 1L-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-specific CD8(+)CD28(+) CTLs. Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN-gamma under the stimulation of H-2K(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 1L-21 and IL-15 can induce a large number of antigen-specific CD8(+)CD28(+) CTLs against the melanoma. Our study provides evidence for a novel adoptive immunotherapy against tumors.