Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer
Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer
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DOI：
10.1158/1078-0432.ccr-04-2062
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发表时间：
2005-05-01
影响因子：
11.5
通讯作者：
Dahut, W
中科院分区：
文献类型：
--
作者：
Gulley, JL;Arlen, PM;Dahut, W
目的：许多临床局限性前列腺癌患者尽管进行了出色的局部治疗，但仍出现生化失败，这可能是由于隐匿性转移性疾病。一种潜在的解决方案是采用耐受性良好的全身治疗（例如疫苗）与局部治疗相结合。 实验设计：我们提出了一项随机 II 期临床试验，旨在确定编码前列腺特异性抗原 (PSA) 的痘病毒疫苗在与临床局限性前列腺癌患者联合放疗时是否可以诱导 PSA 特异性 T 细胞反应。 30 名患者按 2:1 的比例随机分为疫苗加放疗组或仅放疗组。联合组中的患者接受了含有重组痘苗 (rV) PSA 和含有 T 细胞共刺激分子 B7.1 (rV-B7.1) 的 rV 的“初免”疫苗，随后每月接种含有重组鸡痘 PSA 的加强疫苗。疫苗中含有局部粒细胞-巨噬细胞集落刺激因子和低剂量全身性白细胞介素-2。在第四次和第六次疫苗接种之间进行标准外照射放射治疗。结果：联合组 19 名患者中有 17 名完成了全部 8 次疫苗接种，这 17 名患者中的 13 名患者的 PSA 特异性 T 细胞增加了至少 3 倍，而仅放疗组没有检测到增加（P < 0.0005）。还有证据表明，针对疫苗中未发现的明确描述的前列腺相关抗原，T 细胞从头产生，这提供了免疫介导的肿瘤杀伤的间接证据。该疫苗耐受性良好。结论：该疫苗方案可以安全地给予接受局部前列腺癌放射治疗的患者，大多数患者会对疫苗产生 PSA 特异性细胞免疫反应。
Purpose: Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy.Experimental Design: We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a "priming" vaccine with recombinant vaccinia (rV) PSA plus rV containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations.Results: Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated.Conclusion:This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.