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在一名卵巢癌患者中,瘤内重复注射ONCOS-102可引发全身性抗肿瘤CD8 T细胞反应,并在肿瘤部位产生强大的细胞和转录免疫激活。

Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8 T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer.

作者信息

Vassilev L, Ranki T, Joensuu T, Jäger E, Karbach J, Wahle C, Partanen K, Kairemo K, Alanko T, Turkki R, Linder N, Lundin J, Ristimäki A, Kankainen M, Hemminki A, Backman C, Dienel K, von Euler M, Haavisto E, Hakonen T, Juhila J, Jäderberg M, Priha P, Vuolanto A, Pesonen S

机构信息

Oncos Therapeutics ; Helsinki, Finland.

Docrates Cancer Center ; Helsinki, Finland.

出版信息

Oncoimmunology. 2015 Apr 1;4(7):e1017702. doi: 10.1080/2162402X.2015.1017702. eCollection 2015 Jul.

Abstract

Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8 lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8 T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study.

摘要

腺病毒是优秀的免疫治疗剂,具有启动和增强免疫反应的独特能力。重组腺病毒可导致免疫原性癌细胞死亡,并随后释放肿瘤抗原供抗原呈递细胞摄取,从而启动强大的肿瘤特异性免疫。病毒表达的免疫刺激转基因可能会进一步增强这种效应。我们报告了一例38岁患有卵巢3期转移性微乳头浆液性癌的女性病例。她在一项I期研究中接受了表达粒细胞-巨噬细胞集落刺激因子(GMCSF)的溶瘤腺病毒Ad5/3-D24-GMCSF(ONCOS-102)治疗。治疗导致CD8淋巴细胞逐渐浸润到肿瘤中,并同时在全身诱导出多个肿瘤特异性CD8 T细胞群体。在研究开始后20多个月的最新随访中,该患者仍然存活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/4485730/31735e99db0a/koni-04-07-1017702-g001.jpg

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