Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses
Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses
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DOI：
10.1158/1078-0432.ccr-04-0347
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发表时间：
2004-07-15
影响因子：
11.5
通讯作者：
Kufe, D
中科院分区：
文献类型：
--
作者：
Avigan, D;Vasir, B;Kufe, D
目的：树突状细胞（DC）是有效的抗原呈递细胞，具有独特的诱导肿瘤特异性免疫反应的能力。我们进行了一项 I 期试验，其中转移性乳腺癌和肾癌患者接受了通过融合自体肿瘤和 DC 制备的疫苗进行治疗。实验设计：将可触及的肿瘤组织打碎成单细胞悬浮液。自体 DC 是通过白细胞去除术获得的贴壁外周血单核细胞制备的，并在粒细胞巨噬细胞集落刺激因子、白细胞介素 4 和自体血浆中培养。肿瘤细胞和 DC 在聚乙二醇存在下共培养以产生融合体。通过确定共表达肿瘤和 DC 标志物的细胞百分比来量化融合细胞。患者每隔 3 周接种融合细胞疫苗，每周评估毒性，并在疫苗接种完成后 1、3 和 6 个月评估肿瘤反应。结果：为 32 名患者生产了疫苗。 23 名患者接种了 1 x 10(5) 至 4 x 10(6) 融合细胞。融合细胞共表达肿瘤和 DC 抗原并刺激同种异体 T 细胞增殖。没有明显的治疗相关毒性，也没有自身免疫的临床证据。在一部分患者中，疫苗接种导致表达细胞内 IFN-γ 的 CD4 和 CD8+ T 细胞百分比增加，以响应体外暴露于肿瘤裂解物的反应。两名乳腺癌患者表现出疾病消退，包括大胸壁肿块几乎完全缓解。五名肾癌患者和一名乳腺癌患者病情稳定。结论：我们的研究结果表明，对转移性乳腺癌和肾癌患者进行融合细胞疫苗接种是一种可行的、无毒的方法，与诱导免疫和临床抗肿瘤反应相关。
Purpose: Dendritic cells (DCs) are potent antigen-presenting cells that are uniquely capable of inducing tumor-specific immune responses. We have conducted a Phase I trial in which patients with metastatic breast and renal cancer were treated with a vaccine prepared by fusing autologous tumor and DCs.Experimental Design: Accessible tumor tissue was disrupted into single cell suspensions. Autologous DCs were prepared from adherent peripheral blood mononuclear cells that were obtained by leukapheresis and cultured in granulocyte macrophage colony-stimulating factor, interleukin 4, and autologous plasma. Tumor cells and DCs were cocultured in the presence of polyethylene glycol to generate the fusions. Fusion cells were quantified by determining the percentage of cells that coexpress tumor and DC markers. Patients were vaccinated with fusion cells at 3-week intervals and assessed weekly for toxicity, and tumor response was assessed at 1, 3, and 6 months after completion of vaccination.Results: The vaccine was generated for 32 patients. Twenty-three patients were vaccinated with 1 x 10(5) to 4 x 10(6) fusion cells. Fusion cells coexpressed tumor and DC antigens and stimulated allogeneic T-cell proliferation. There was no significant treatment-related toxicity and no clinical evidence of autoimmunity. In a subset of patients, vaccination resulted in an increased percentage of CD4 and CD8+ T cells expressing intracellular IFN-gamma in response to in vitro exposure to tumor lysate. Two patients with breast cancer exhibited disease regressions, including a near complete response of a large chest wall mass. Five patients with renal carcinoma and one patient with breast cancer had disease stabilization.Conclusions: Our findings demonstrate that fusion cell vaccination of patients with metastatic breast and renal cancer is a feasible, nontoxic approach associated with the induction of immunological and clinical antitumor responses.