Cytotoxic CD8(+) T cells are key effectors in the
immunotherapy of malignant and
viral diseases. However, autologous T cell responses to
tumor antigens presented by self-MHC are usually weak and ineffective. Allo-restricted T cells represent a potent source of
tumor-specific T cells for adoptive immunotherapy. This study reports in vivo anti-
melanoma efficacy of the pTRP2-specific allo-restricted CTLs expanded from the BALB/c 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 allo-restricted 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 the allo-restricted CTLs specific for
malignant melanoma expanded by the aAPCs can mediate effective anti-
melanoma response in vivo. These results suggested that the specific allo-restricted CTLs expanded by aAPCs coated with an MHC-Ig/
peptide complex, anti-CD28 antibody, 4-1BBL and CD83 could be a potential option of specific
immunotherapy for patients with
malignant melanoma.