CD40-activated B cells can be generated in high number and purity in cancer patients: analysis of immunogenicity and homing potential
CD40-activated B cells can be generated in high number and purity in cancer patients: analysis of immunogenicity and homing potential
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DOI：
10.1111/j.1365-2249.2008.03820.x
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发表时间：
2009-02-01
影响因子：
4.6
通讯作者：
von Bergwelt-Baildon, M. S.
中科院分区：
文献类型：
--
作者：
Kondo, E.;Gryschok, L.;von Bergwelt-Baildon, M. S.
细胞佐剂，如树突状细胞（DC）是肿瘤免疫治疗的重点。在dc疫苗试验中，经常观察到肿瘤抗原特异性免疫的诱导，并报道了有充分证据的临床反应。然而，总体响应率低于3%，因此正在研究替代策略。cd40活化的B细胞（CD40-B）以前被认为是一种有趣的替代方法，因为它们有效地呈递抗原，并且可以通过少量外周血中的几个log进行扩增。为了确定细胞疫苗的核心技术挑战，我们对来自dc肿瘤疫苗试验的502例患者进行了单例分析，并确定了至少三个导致其效率有限的因素：(1)缺乏细胞数量；(2)缺乏纯度证明，因此旁观者细胞的高污染；(3)缺乏质量控制，因此重要的表面分子如主要组织相容性复合体（MHC）和趋化因子受体的表达不均匀或未知。基于这些发现，我们重新评估了CD40-B方法在癌症患者中的应用。在这里，我们发现来自癌症患者的B细胞增殖与在健康供体中观察到的相同。2周后纯度总是在90%左右，并保持稳定数周。它们具有相当的抗原提呈能力，由表型和同种异体混合淋巴细胞反应决定。在所有样本中检测到CCR7和CD62L的表达，B细胞向相关归巢趋化因子迁移。综上所述，来自癌症患者的CD40-B细胞可以以高纯度扩增到几乎无限数量，并且在抗原呈递和迁移特性方面具有完整的功能。
Cellular adjuvants such as dendritic cells (DC) are in the focus of tumour immunotherapy. In DC-vaccine trials, induction of tumour antigen-specific immunity is observed frequently and well-documented clinical responses have been reported. However, the overall response rate is less than 3%, therefore alternative strategies are being investigated. CD40-activated B cells (CD40-B) have been characterized previously as an interesting alternative because they present antigen efficiently and can be expanded by several logs from small amounts of peripheral blood. To determine the central technical challenges of cell-based vaccines we performed a single-patient analysis of 502 patients from DC-based tumour vaccine trials and identified at least three factors contributing to their limited efficiency: (1) lack of cell numbers; (2) lack of documented purity thus high contamination of bystander cells; and (3) lack of quality control and thus heterogeneous or unknown expression of important surface molecules such as major histocompatibility complex (MHC) and chemokine receptors. Based on these findings we re-evaluated the CD40-B approach in cancer patients. Here, we show that proliferation of B cells from cancer patients is equivalent to that observed in healthy donors. Purity is always > 90% after 2 weeks and remains stable for several weeks. They have comparable antigen-presenting capability determined phenotypically and by allogeneic mixed lymphocyte reaction. Expression of CCR7 and CD62L was detected in all samples and B cells migrated towards the relevant homing chemokines. Taken together, CD40-B cells from cancer patients can be expanded in virtually unlimited numbers at high purity and full function concerning antigen-presentation and migratory properties.