[CTLs induced by hTERT-related multiepitope peptide-sensitived mDCs specifically kill HLA-A24+ tumor cells]

To study the antigen specific anti-tumor effect of cytotoxic T lymphocytes(CTLs), which was induced by human telomerase reverse transcriptase (hTERT)-related multiple epitope peptides impulsed myeloid dendritic cells(mDCs), against human leukocyte antigen (HLA)-A24(+) tumor cells.

Four branches of multiple antigen peptides (MAPs) of hTERT epitopes and three separate peptides were solid-phase artificially synthesized, phlebotomize peripheral blood from HLA-A24(+) healthy volunteers, sorted the blood through MACS MicroBeads and cultured mDCs, Nylon fiber column purified T lymphocytes, mDCs impulsed with each type of peptides were co-cultured with T lymphocytes to induce CTLs specifically killing effect, and the resultant CTLs were used as effector cells, SMMC-7721 with hTERT and HLA-A24 positive and SKOV3 which are hTERT-positive but HLA-A24-negative tumor cells were used as target cells. The level of human IL-12, TNF-α in the culture supernatant was determined by ELISA. Flow cytometry assay was used to assess the killing ability of CTLs against tumor cells.

MAPs of hTERT epitopes including I540 (ILAKFLHWL), V461 (VYGFVRACL), L766 (LTDLQPYMRQFVAHL) and three separate peptides could impulse mDCs and then induce CTLs to specifically kill SMMC-7721, CTLs induced by MAPs had stronger cytotoxic effect compared with three separate peptides mixed(P < 0.05).

mDCs-impulsed with hTERT-associated MAPs can induce production and proliferation of allogenic CTLs, which show antigen specific anti-tumor effect against HLA-A24(+) tumor cells. This result has significantly meaning in tumor immunotherapy.