Transfer Therapy Cancer Regression in Patients Receiving Cell Lymphocyte Clonotypes Correlates with Cutting Edge: Persistence of Transferred
Transfer Therapy Cancer Regression in Patients Receiving Cell Lymphocyte Clonotypes Correlates with Cutting Edge: Persistence of Transferred
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J. Powell;Steven A Rosenberg El-Gamil;Yong F Li;Juhua Zhou;Jianping Huang;Daniel Paul;F. Robbins;M. Dudley;J. Wunderlich;Mona
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作者：
J. Powell;Steven A Rosenberg El-Gamil;Yong F Li;Juhua Zhou;Jianping Huang;Daniel Paul;F. Robbins;M. Dudley;J. Wunderlich;Mona
移植的自体成熟淋巴细胞在人体中缺乏持久性一直是有效细胞移植疗法应用的主要限制。在13例转移性黑色素瘤患者中进行的初步临床试验的结果表明，在过继转移活化的肿瘤反应性T细胞之前进行非清髓性化疗的预处理可增强肿瘤消退，并增加客观临床反应的总体发生率。本报告通过分析从25例接受本方案治疗的患者中获得的样本中表达的TCR（cid：1）链V区基因产物，研究T细胞持久性和肿瘤消退之间的关系。序列分析表明，有一个显着的相关性肿瘤消退和过继转移的T细胞克隆的外周血中的持久性的程度，表明T细胞持久性不足可能是一个主要因素限制过继免疫治疗的反应。免疫学杂志，2004，173：7125-7130.用VectorNTIAlignX方法（InvitrogenLifeTechnologies，卡尔斯巴德，CA）将克隆的序列与已知的TRBV基因序列进行比对，鉴定编码表达的TRBV产物的种系基因，并比较将TRBV基因连接到D（cid：1）和J（cid：1）区所产生的高度可变的序列，以鉴定T细胞克隆型。
The lack of persistence of transferred autologous mature lymphocytes in humans has been a major limitation to the application of effective cell transfer therapies. The results of a pilot clinical trial in 13 patients with metastatic melanoma suggested that conditioning with nonmyeloablative chemotherapy before adoptive transfer of activated tumor-reactive T cells enhances tumor regression and in-creases the overall rates of objective clinical responses. The present report examines the relationship between T cell persistence and tumor regression through analysis of the TCR (cid:1) -chain V region gene products expressed in samples obtained from 25 patients treated with this protocol. Sequence analysis demonstrated that there was a significant correlation between tumor regression and the degree of persistence in peripheral blood of adoptively transferred T cell clones, suggesting that inadequate T cell persistence may represent a major factor limiting responses to adoptive immunotherapy. The Journal of Immunology, 2004, 173: 7125–7130. CA) to amplify the TRBV region se-quencesexpressedbypolyclonalTILsamples.ThegermlinegenesthatencodedtheexpressedTRBVproductswereidentifiedbyaligningtheclonedsequenceswiththeknownTRBVgenesequencesusingtheVectorNTIAlignXprotocol(InvitrogenLifeTechnologies,Carlsbad,CA)andthehighlyvariablesequencesthatresultedfromjoiningtheTRBVgenestotheD (cid:1) and J (cid:1) regions were then compared to identify T cell clonotypes.