Cytotoxic CD8(+) T cells are key effectors in the
immunotherapy of malignant and
viral diseases. However, the lack of efficient methods for their in vitro priming and expansion has become a bottleneck to the development of
vaccines and adoptive transfer strategies. Synthetic artificial antigen-presenting cells (aAPCs) are now emerging as an attractive tool for eliciting and expanding CTL responses. This study reported a novel approach for targeting
malignant melanoma with pTRP2-specific cytotoxic T lymphocytes (CTLs) expanded from the C57BL/6 splenocytes by multiple stimulations with aAPCs made by coating H-2K(b)-Ig/pTRP2 dimeric complexes, anti-CD28 antibody, 4-1BBL molecules and CD83 molecules to cell-sized
latex beads. The induced CTLs exhibited specific lysis against RMA-S cells pulsed with the
peptide pTRP2 and H-2K(b+)
melanoma cells expressing TRP2, while a murine
Lewis lung carcinoma cell line 3LL could not be recognized by the CTLs. The
peptide-specific activity was inhibited by anti-H-2K(b)
monoclonal antibody Y3. Adoptive Transfer of CTLs specific for
malignant melanoma expanding by the aAPCs can mediate effective anti-
melanoma response. These results suggested the bead-based aAPCs coated with an MHC-Ig/
peptide complex, anti-CD28 antibody, 4-1BBL and CD83 could provide a useful tool for the reproducible expansion of specific CTLs for adoptive immunotherapy.