Efficacy of polypeptide-loaded dendritic cells in combination with cytokine- induced killer cells on hormone refractory prostate cancer
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Abstract:
Objective:To investigate the efficacy of polypeptide-loaded dendritic cells (DCs) in combination with cytokine-induced killer cells (CIKs) against hormone refractory metastatic prostate cancer (HRPC) patients. Methods: Twenty-six HLA-A2+ patients with HRPC were enrolled from the Department of Chinese Traditional and Western Medicine of the Wuxi No.4 People’s Hospital. Peripheral blood mononuclear cells (PBMCs) were separated, and the adherent cells were induced into DCs by GM-CSF and IL-4. Then DCs were loaded with three peptides (prostate specific antigen, PSA; prostatic acid phosphatase, PAP; prostate specific membrane antigen, PSMA) to prepare DC vaccine and were injected intracutaneously. The un-adherent cells of PBMCs were induced into CIK by IFN-γ, IL-2, CD3 monoclonal antibody and IL-1, and were injected intravenously. Delayed type hypersensitivity (DTH) was detected one week after treatment, and cytokine and PSA in serum were determined before and after treatment. The short-term efficacy was evaluated 4 weeks after treatment. Results: DC-CIK therapy was well tolerated in 26 HRPC patients. The serum IL-2, IL-12, and IFN-γ levels after therapy were significantly increased (increased 65.07%, 67.69% and 12538%, P<0.05 or P<001), while TNF-α and IL-10 levels were unchanged. The positive rate of DTH was 43.5% (10/23). The proportion of CD8+IFNγ+ cells after therapy was significantly increased (\[8.95±2.74\]% vs \[0.39±015\]%, P<0.01). A decrease of PSA (13% to 66%) was observed in 8 of 26 patients. The short-term efficacy of 26 HRPC patients was evaluated, with 3 PR, 4 PD, and 19 SD after treatment, and no severe adverse reaction was observed. Conclusion: The polypeptide-loaded DC in combination with CIK therapy can elicit specific immune responses in HRPC patients, and induce type I cytokine secretion with well short-term clinical efficacy, indicating that DC-CIK therapy is a safe treatment for HRPC.
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Project supported by the Scientifical Guidance Plan of Science and Technology Bureau of Wuxi