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目的:观察前列腺特异性抗原(PSA)、前列腺特异性膜抗原(PSMA)与前列腺酸性磷酸酶(PAP)多肽联合致敏自体树突状细胞(DC)治疗激素难治性前列腺癌(HRPC)的安全性与有效性。方法:选择HLA-A201阳性HRPC患者16例,分离患者外周血中单核细胞,加入重组人粒细胞集落刺激因子(rhGM-CSF)与白介素(rhIL-4)诱导成DC。用PSA(KLQCVDLHV)、PSMA(ALDVYNGLL)与PAP(LLHETDSAV)3种多肽联合冲击DC后近腹股沟淋巴结富集区皮内多点接种致敏DC,隔周1次,共进行4次接种,于最后1次接种后1～2周内进行免疫学与近期临床疗效的监测。结果:未见1例出现Ⅱ级以上不良反应(寒颤、发烧、注射部位红肿、皮疹等)。患者接种DC后外周血中IL-2、IL-12和IFN-γ水平呈明显上升趋势(P<0.01);迟发型超敏反应(DTH)试验阳性率为36.4%(4/11);5例患者外周抗原特异性IFN-γ+CD8+T细胞比例明显增加(5/11);6例患者PSA水平下降(6/16);1例患者腹腔积液减少;1例患者颈部淋巴结转移灶缩小。3例患者临床反应达到部分缓解(PR),7例患者稳定(SD),6例患者进展(PD)。结论:PSA、PSMA和PAP多肽联合负载自体DC免疫治疗方法可明显改善HRPC患者免疫功能,有效激发特异性T细胞免疫应答,控制并缓解病情,是治疗晚期HRPC的一种安全与有效的手段。
OBJECTIVE: To observe the effect of autologous dendritic cells (DCs) sensitized with prostate specific antigen (PSA), prostate specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP) polypeptide on hormone refractory prostate cancer (HRPC) Safety and effectiveness. METHODS: Sixteen patients with HLA-A201-positive HRPC were selected and mononuclear cells (PBMCs) were isolated from peripheral blood of patients with HLA-A201 infection. DCs were induced by adding recombinant human granulocyte colony-stimulating factor (rhGM-CSF) and interleukin (rhIL-4) DCs were inoculated with PSA (KLQCVDLHV), PSMA (ALDVYNGLL) and PAP (LLHETDSAV) in combination with multiple peptides in the inguinal lymph node enrichment zone to inoculate the DCs once every other week for a total of 4 inoculations. Immunization and clinical efficacy monitoring within 1 to 2 weeks after inoculation. Results: No one case of grade Ⅱ or more adverse reactions (chills, fever, inflamed injection site, rash, etc.). The levels of IL-2, IL-12 and IFN-γ in peripheral blood were significantly increased in DC patients (P <0.01). The positive rate of delayed type hypersensitivity (DTH) test was 36.4% (4/11) The proportion of peripheral antigen-specific IFN-γ + CD8 + T cells was significantly increased (5/11) in 6 cases; the PSA level was decreased in 6 cases (6/16); one case was reduced ascites; one case of cervical lymph node metastasis Zaozhong. Three patients achieved partial response (PR), seven patients were stable (SD), and six patients progressed (PD). CONCLUSIONS: PSA, PSMA and PAP peptides combined with autologous DC immunotherapy can significantly improve the immune function of HRPC patients, effectively stimulate specific T cell immune response, control and relieve the disease, which is a safe and effective method for the treatment of advanced HRPC.