Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients
Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients
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DOI：
10.1016/j.ijrobp.2005.11.009
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发表时间：
2006-05-01
影响因子：
7
通讯作者：
Thompson, Timothy C.
中科院分区：
文献类型：
--
作者：
Fujita, Tetsuo;Teh, Bin S.;Thompson, Timothy C.
目的：探索长期的免疫反应后，结合radio-gene-hormonal therapeutic.Methods和材料：33例前列腺特异性抗原10或更高或Gleason评分为7或更高或临床阶段T2 b至T3的患者进行了基因治疗，包括3个单独的前列腺内注射AdHSV-tk的第0，56和70天。每次注射后2周的伐昔洛韦。在第二次注射AdHSV-tk后2天进行调强放射治疗，持续7周。激素治疗在第0天开始，持续4个月或2.3年。在治疗前、治疗期间和治疗后采集血样。结果：中位随访时间为26个月（范围，4-48个月）。DR（+）CD 8（+）T细胞的平均百分比在8个月内的所有时间点均升高。DR（+）CD 4（+）T细胞的平均百分比增加较晚，持续时间更长，直到12个月。长期（2.3年）使用激素治疗并没有影响任何淋巴细胞population.Conclusions的百分比：持续的长期（长达8至12个月）的全身T细胞反应后，联合放射基因激素治疗前列腺癌。长期使用激素治疗不能抑制这种反应。这些结果表明了持续激活细胞介导的抗癌免疫应答的潜力。(c)2006年爱思唯尔公司
Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy.Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or-clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS).Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR(+)CD8(+) T cells were increased at all timepoints up to 8 months. The mean percentages of DR(+)CD4(+) T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population.Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer. (c) 2006 Elsevier Inc.