McNeel Douglas G, Dunphy Edward J, Davies James G, Frye Thomas P, Johnson Laura E, Staab Mary Jane, Horvath Dorothea L, Straus Jane, Alberti Dona, Marnocha Rebecca, Liu Glenn, Eickhoff Jens C, Wilding George
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Department of Biostatistics, University of Wisconsin, Madison, WI, USA.
J Clin Oncol. 2009 Sep 1;27(25):4047-54. doi: 10.1200/JCO.2008.19.9968. Epub 2009 Jul 27.
Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer.
Twenty-two patients were treated in a dose-escalation trial with 100 microg, 500 microg, or 1,500 microg plasmid DNA, coadministered intradermally with 200 microg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment.
No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFN gamma-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054).
The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.
前列腺酸性磷酸酶（PAP）是一种前列腺肿瘤抗原。我们之前已证明，编码PAP的DNA疫苗可在啮齿动物中引发抗原特异性CD8⁺T细胞。我们在此报告一项针对D0期前列腺癌患者使用编码人PAP的DNA疫苗进行的I/IIa期试验结果。
22名患者参与了剂量递增试验，分别接受100微克、500微克或1500微克质粒DNA治疗，同时皮内注射200微克粒细胞巨噬细胞集落刺激因子作为疫苗佐剂，每14天注射一次，共注射六次。所有患者在治疗后观察1年。
未观察到明显不良事件。酶联免疫斑点法检测显示，22名患者中有3名（14%）在疗程结束后立即产生了分泌PAP特异性干扰素γ的CD8⁺T细胞。22名患者中有9名（41%）出现了PAP特异性CD4⁺和/或CD8⁺T细胞增殖。未检测到对PAP的抗体反应。总体而言，观察到前列腺特异性抗原（PSA）倍增时间从治疗前的中位数6.5个月增加到治疗期间的8.5个月（P = .033），在治疗后1年期间为9.3个月（P = .054）。
编码PAP的DNA疫苗安全，能引发抗原特异性T细胞反应，且可能与PSA倍增时间延长有关，这表明有必要开展一项多机构II期试验来评估其临床疗效。
