HLA type-independent generation of antigen-specific T cells for adoptive immunotherapy
HLA type-independent generation of antigen-specific T cells for adoptive immunotherapy
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DOI：
10.1002/eji.200526230
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发表时间：
2005-07-01
影响因子：
5.4
通讯作者：
Reinke, P
中科院分区：
文献类型：
--
作者：
Hammer, MH;Meyer, S;Reinke, P
抗原特异性T细胞过继免疫疗法已成功用于某些感染性疾病和癌症的治疗。虽然更多的患者可能受益于T细胞治疗，但其更频繁的使用受到当前T细胞生成策略的限制。最常用的基于多肽的方法依赖于相关表位的知识。因此，T细胞不能用于抗原表位未知的疾病或具有不利的人类白细胞抗原类型的患者。我们开发了一种基于多肽的方法，用于针对各种蛋白质产生不依赖于人类白细胞抗原类型的特定T细胞。它是基于短时刺激的多肽库，它覆盖了给定蛋白质的大多数CD4(+)和CD8(+)T细胞表位。这一过程不需要事先了解表位，因为文库完全是根据蛋白质的氨基酸序列合成的。刺激之后是免疫磁性选择激活的干扰素-γ分泌细胞和非特异性扩增。为了评估该方案，我们产生了针对具有良好特性的抗原--人巨细胞病毒磷酸蛋白65(Pp65)的自体T细胞。产生的T细胞系由pp65特异性的CD4(+)和CD8(+)淋巴细胞组成，表现出抗原特异性的杀伤和增殖。该方案结合了基于多肽的方法的生物安全性和HLA型独立性，并可能有助于促进未来的过继免疫治疗。
Adoptive immunotherapy with antigen-specific T cells has been successfully used to treat certain infectious diseases and cancers. Although more patients may profit from T cell therapy, its more frequent use is restricted by limitations in current T cell generation strategies. The most commonly applied peptide-based approaches rely on the knowledge of relevant epitopes. Therefore, T cells cannot be generated for diseases with unknown epitopes or for patients with unfavorable HLA types. We developed a peptide-based approach for HLA type-independent generation of specific T cells against various proteins. It is based on short-time stimulation with peptide libraries that cover most CD4(+) and CD8(+) T cell epitopes of given proteins. The procedure requires no prior knowledge of epitopes because libraries are synthesized solely on the basis of the protein's amino acid sequence. Stimulation is followed by immunomagnetic selection of activated IFN-gamma-secreting cells and nonspecific expansion. To evaluate the protocol, we generated autologous T cells specific for a well-characterized antigen, the human cytomegalovirus phosphoprotein 65 (pp65). Generated T cell lines consisted of pp65-specific CD4(+) and CD8(+) lymphocytes that displayed antigen-specific killing and proliferation. The protocol combines the biosafety of peptide-based approaches with HLA type independence and may help to advance adoptive immunotherapy in the future.