Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2
Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2
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DOI：
10.1200/jco.1997.15.2.796
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发表时间：
1997-02-01
影响因子：
45.3
通讯作者：
Shu, SY
中科院分区：
文献类型：
--
作者：
Chang, AE;Aruga, A;Shu, SY
目的：在临床前研究中，我们报道了用细菌佐剂对肿瘤细胞进行体内疫苗接种诱导淋巴结（LN）免疫T细胞的能力。这些LN细胞可以在体外被激活和扩增，从而成功地对已建立的肿瘤进行免疫治疗。我们已经应用这些方法在晚期黑色素瘤和肾细胞癌（RCC）患者中产生疫苗引发的LN进行治疗。材料与方法：采用经辐照的自体肿瘤细胞与卡介苗混合接种。7天后，取出引流LN，用抗cd3单克隆抗体（mAb）激活，然后扩增白细胞介素-2 （IL-2）。激活的LN细胞静脉注射（IV），同时给予IL-2。结果：共评估了23例患者（11例黑色素瘤和12例RCC）。疫苗引发的LN在体外扩增，每位患者平均给予8.4 x 10（10）个细胞。在评估的20例患者中，15例通过活化的LN细胞表现出最小的自体肿瘤细胞毒性，其余的介导非特异性细胞毒性。相比之下，大多数活化的LN细胞对自体而非异体肿瘤刺激表现出高度特异性的粒细胞-巨噬细胞集落刺激因子（GM-CSF）和干扰素γ (ifn - γ)释放。这种肿瘤特异性细胞因子释放被发现是主要组织相容性复合体（MHC） i类限制，这表明CD8（+）细胞参与其中。在11名黑色素瘤患者中，有1人对肿瘤有部分反应。在12例RCC患者中，2例完全缓解，2例部分缓解。治疗后迟发性超敏反应（DTH）反应性增强与肿瘤消退有明显的趋势（P = 0.066）。结论：肿瘤疫苗可诱导针对黑素瘤和肾细胞癌引流LN的免疫特异性t细胞反应。抗cd3 /IL-2激活LN细胞可以可靠地用于临床治疗，并且似乎在转移性RCC患者中具有活性。(C) 1997年由美国临床肿瘤学会。
Purpose: In preclinical studies, we have reported the ability to induce immune T cells in lymph nodes (LN) primed by in vivo vaccination with tumor cells admired with a bacterial adjuvant. These LN cells can be activated and expanded ex vivo for the successful immunotherapy of established tumors. We have applied these methods to generate vaccine-primed LN in patients with advanced melanoma and renal cell cancer (RCC) for therapy.Materials and Methods: Irradiated autologous tumor cells admixed with bacille Calmette-Guerin (BCG) were used to vaccinate patients. Seven days later, draining LN were removed for activation with anti-CD3 monoclonal antibody (mAb) followed by expansion in interleukin-2 (IL-2). Activated LN cells were administered intravenously (IV) with the concomitant administration of IL-2.Results: A total of 23 patients were evaluated (11 melanoma and 12 RCC). Vaccine-primed LN were expanded ex vivo with a mean of 8.4 x 10(10) cells administered per patient. Among 20 patients assessed, 15 demonstrated minimal cytotoxicity of autologous tumor cells by the activated LN cells, with the remaining mediating nonspecific cytotoxicity. By contrast, a majority of the activated LN cells showed highly specific release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-gamma) to autologous but not allogeneic tumor stimulation. This tumor-specific cytokine release was found to be major histocompatibility complex (MHC) class I-restricted, which indicates the involvement of CD8(+) cells. Among 11 melanoma patients, one had a partial tumor response. Among 12 RCC patients, two had complete and two partial responses. A trend (P = .066) between the enhancement of delayed-type hypersensitivity (DTH) reactivity to autologous tumor after therapy and tumor regression was observed.Conclusion: Tumor vaccines can be used to induce immunologically specific T-cell responses against melanoma and RCC in draining LN. Anti-CD3/IL-2 activation of primed LN cells can be reliably performed for clinical therapy and appears to have activity in patients with metastatic RCC. (C) 1997 by American Society of Clinical Oncology.