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具有体外抗肿瘤活性的同种异体爱泼斯坦-巴尔病毒(EBV)特异性细胞毒性T细胞的过继转移增强了一名EBV相关鼻咽癌患者的LMP2特异性免疫反应。

Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma.

作者信息

Comoli P, De Palma R, Siena S, Nocera A, Basso S, Del Galdo F, Schiavo R, Carminati O, Tagliamacco A, Abbate G F, Locatelli F, Maccario R, Pedrazzoli P

机构信息

Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy.

出版信息

Ann Oncol. 2004 Jan;15(1):113-7. doi: 10.1093/annonc/mdh027.

DOI:10.1093/annonc/mdh027
PMID:14679129
Abstract

BACKGROUND

The outcome of patients with nasopharyngeal carcinoma (NPC) presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein-Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and methods A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated.

RESULTS

CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity.

CONCLUSIONS

Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.

摘要

背景

以晚期疾病形式出现或传统放化疗失败的鼻咽癌(NPC)患者预后较差。因此,需要额外的有效、低毒治疗形式来改善NPC的预后。由于NPC几乎普遍与EB病毒(EBV)相关,用EBV特异性细胞毒性T淋巴细胞(CTL)进行细胞免疫治疗可能是一种成功的治疗策略。

患者和方法

一名复发性NPC患者,对传统治疗无效,接受了从人类白细胞抗原相同的同胞体外重新激活的EBV特异性CTL的挽救性过继免疫治疗。评估了免疫治疗前后的EBV特异性免疫以及肿瘤中的T细胞库。

结果

CTL转移耐受性良好,疾病得到了暂时稳定。此外,尽管同种异体CTL在体内持续时间较短,但免疫治疗诱导了内源性肿瘤浸润性CD8 + T淋巴细胞的显著增加以及潜伏膜蛋白2特异性免疫的长期增加。

结论

该患者获得的初步数据表明,EBV特异性CTL是安全的,可能在体外对NPC肿瘤细胞发挥特异性杀伤作用,并在体内诱导抗肿瘤作用。

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