In vivo manipulation of Vγ9Vδ2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients
In vivo manipulation of Vγ9Vδ2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients
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DOI：
10.1111/j.1365-2249.2010.04167.x
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发表时间：
2010-08-01
影响因子：
4.6
通讯作者：
Hayday, A. C.
中科院分区：
文献类型：
--
作者：
Meraviglia, S.;Eberl, M.;Hayday, A. C.
γ δ T细胞的有效抗肿瘤活性促进了对癌症患者施用γ δ激动剂的方案的发展。小型I期试验的令人鼓舞的结果推动了更清楚地描述这种方法在未满足的临床需求（如转移性癌）中的应用的努力。为了检验这种方法在乳腺癌中的应用，进行了一项I期试验，其中将唑来膦酸盐（一种V γ 9V δ 2 T细胞激动剂）加上低剂量白细胞介素（IL）-2给予10名治疗终末的晚期转移性乳腺癌患者。治疗耐受性良好，并促进所有患者中V γ 9V δ 2 T细胞的效应子成熟。然而，出现了临床结果与外周V γ 9V δ 2 T细胞数量的统计学显著相关性，因为7名未能维持V γ 9V δ 2 T细胞的患者显示出进行性临床恶化，而3名维持稳定外周V γ 9V δ 2细胞群体的患者显示出CA 15 -3水平下降，并显示出1例部分缓解和2例稳定疾病，分别在前列腺癌早期试验的背景下，这些数据强调了V γ 9V δ 2 T细胞状态与降低癌症进展的强烈联系，并表明唑来膦酸盐加低剂量IL-2提供了一种新的，安全的和可行的方法，以增强治疗难治性晚期乳腺癌患者的亚组。
P>The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V gamma 9V delta 2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V gamma 9V delta 2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral V gamma 9V delta 2 T cell numbers emerged, as seven patients who failed to sustain V gamma 9V delta 2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral V gamma 9V delta 2 cell populations showed declining CA15-3 levels and displayed one instance of partial remission and two of stable disease, respectively. In the context of an earlier trial in prostate cancer, these data emphasize the strong linkage of V gamma 9V delta 2 T cell status to reduced carcinoma progression, and suggest that zoledronate plus low-dose IL-2 offers a novel, safe and feasible approach to enhance this in a subset of treatment-refractory patients with advanced breast cancer.