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目的:研究多肽负载树突状细胞(dendritic cell,DC)联合细胞因子诱导的杀伤细胞(cytokine-induced killer cell,CIK)对激素难治性前列腺癌(hormone refractory metastatic prostate cancer,HRPC)患者免疫治疗的效果。方法:选择无锡市第四人民医院中西医结合科收治的HLA-A2+HRPC患者26例,分离外周血单个核细胞,其中贴壁细胞经GM-CSF、IL-4联合诱导培养为成熟DC,负载前列腺癌特异性抗原(prostate specific antigen,PSA)、前列腺酸性磷酸酶(prostatic acid phosphatase,PAP)、前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)三个多肽,制备成DC疫苗,经患者腹股沟皮内注射;未贴壁细胞经IFN-γ、IL-2、抗CD3单抗、IL-1体外诱导培养成CIK,经静脉回输给患者。在治疗后1周进行迟发型超敏反应(delayed type hypersensitivity,DTH)检测,在患者治疗前后进行血清中细胞因子和PSA检测,治疗结束后4周进行短期疗效评价。结果:26例HRPC患者对DC联合CIK治疗的耐受良好。治疗后患者血清中IL-2、IL-12、IFN-γ水平较治疗前显著升高(上升幅度分别为65.07%、67.69%和125.38%,P<0.05或P<0.01),TNF-α和IL-10水平变化不大;DTH的阳性率为43.5%(10/23);7例患者的CD8+IFN-γ+T细胞比例较治疗前显著提高[(8.95±2.74)%vs(0.39±0.15)%,P<0.01];8/26例患者的PSA下降,降幅为13%~66%。26例患者短期疗效评价,3例PR、4例PD、19例SD,所有患者治疗中未出现明显不良反应。结论:多肽负载DC联合CIK治疗HRPC能激发患者的免疫应答、诱导Th1型细胞因子的分泌,近期疗效良好,是一种安全的治疗方法。
OBJECTIVE: To study the effect of polypeptide-loaded dendritic cells (DCs) combined with cytokine-induced killer cells (CIK) on immunotherapy in patients with hormone refractory metastatic prostate cancer (HRPC) Effect. Methods: Totally 26 HLA-A2 + HRPC patients were selected from Department of Integrated Traditional Chinese and Western Medicine in Fourth People’s Hospital of Wuxi. Peripheral blood mononuclear cells were isolated. Adherent cells were induced to mature DCs by GM-CSF and IL-4. DCs were prepared by loading three peptides: prostate specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate specific membrane antigen (PSMA) The groin was injected intradermally. The non-adherent cells were induced to CIK by IFN-γ, IL-2, anti-CD3 monoclonal antibody and IL-1 in vitro. One week after treatment, delayed type hypersensitivity (DTH) was used to detect serum cytokines and PSA before and after treatment. Short-term efficacy was evaluated 4 weeks after the end of treatment. Results: Twenty-six HRPC patients were well tolerated by DC combined with CIK. The levels of IL-2, IL-12 and IFN-γ in serum of patients after treatment were significantly higher than those before treatment (65.07%, 67.69% and 125.38% respectively, P <0.05 or P <0.01) The positive rate of DTH was 43.5% (10/23). The proportion of CD8 + IFN-γ + T cells in 7 patients was significantly higher than that before treatment [(8.95 ± 2.74)% vs (0.39 ± 0.15)%, P <0.01]. The PSA of 8/26 patients decreased by 13% -66%. Short-term efficacy evaluation of 26 patients, PR in 3 cases, PD in 4 cases and SD in 19 cases showed no obvious adverse reactions in all patients. Conclusion: Peptide-loaded DC combined with CIK in the treatment of HRPC can stimulate the immune response of patients and induce the secretion of Th1-type cytokines. It has a good short-term curative effect and is a safe treatment.