Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors
Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors
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tag7/PGRP-S基因修饰的自体肿瘤细胞对播散性实体瘤患者进行基因治疗的I/II期试验
DOI：
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
G. Georgiev
中科院分区：
文献类型：
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作者：
V. Moiseyenko;Danilov Ao;I. Baldueva;Danilov Ab;N. V. Tyukavina;Larin Ss;S. Kiselev;R. Orlova;Anisimov Vv;A. Semenova;L. A. Shchekina;Gafton Gi;Kochnev Va;A. Barchuk;Kanaev Sv;K. Hanson;G. Georgiev
背景：使用基因修饰的自体肿瘤细胞似乎是一种有前途的癌症治疗方法。将tag 7/PGRP-S基因导入恶性黑色素瘤和肾癌细胞制备自体疫苗，并进行I/II期临床试验，以确定该疫苗的可行性、安全性和抗肿瘤作用。患者和方法：21例患者（17例播散性恶性黑色素瘤和4例转移性肾细胞癌）入组本研究。所有病例在治疗前均进行了细胞减灭术。用tag 7/PGRP-S基因转染自体肿瘤细胞，每3周照射并皮内注射。结果：所有患者均对疫苗接种耐受良好，无临床显著毒性体征。在48%的病例中观察到迟发型超敏反应。在95%的患者中观察到抗肿瘤免疫应答。无完全或部分缓解;然而，1例肾细胞癌患者出现轻微缓解。在8例患者中观察到肿瘤疾病的稳定（7例恶性黑色素瘤和1例肾细胞癌）。肿瘤进展的中位时间为3个月。结论：这里提出的方法似乎耐受性良好，并产生了一些持久的临床效果。需要进一步的研究来确定对免疫激活的有希望的作用是否会导致恶性黑色素瘤和肾细胞癌患者的实际临床获益。
Background: The use of genetically modified autologous tumor cells appears to be a promising approach for cancer therapy. A phase I/II trial was undertaken to define the feasibility, safety and antitumor effects of the autologous vaccine prepared by transferring tag7/PGRP-S gene into malignant melanoma and renal cell carcinoma cells. Patients and methods: Twenty-one patients (17 with disseminated malignant melanoma and four with metastatic renal cell carcinoma) were enrolled in this study. Cytoreduction was performed in all cases prior to therapy. Autologous tumor cells were transfected with the tag7/PGRP-S gene, irradiated and injected intradermally every 3 weeks. Results: Vaccinations were well tolerated by all patients, without clinically significant signs of toxicity. Delayed-type hypersensitivity was observed in 48% of cases. Antitumor immune response was observed in 95% of patients. There were no complete or partial responses; however, a minor response was achieved in one patient with renal cell carcinoma. The stabilization of neoplastic disease was observed in eight patients (seven with malignant melanoma and one with renal cell carcinoma). Median time to tumor progression was 3 months. Conclusions: The approach suggested here appears to be well tolerated and produces a number of durable clinical effects. Further studies are required to determine whether promising effects on immune activation will result in an actual clinical benefit for patients with malignant melanoma and renal cell carcinoma.
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DOI：
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发表时间：
2003
期刊：
Cancer immunity
影响因子：
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作者：
J. Mollick;F. Hodi;R. Soiffer;L. Nadler;G. Dranoff
通讯作者：
J. Mollick;F. Hodi;R. Soiffer;L. Nadler;G. Dranoff
影响因子：
45.3
作者：
BERD, D;MAGUIRE, HC;MASTRANGELO, MJ
通讯作者：
MASTRANGELO, MJ
影响因子：
4.2
作者：
Chang, AE;Li, Q;Nickoloff, BJ
通讯作者：
Nickoloff, BJ
影响因子：
45.3
作者：
Soiffer, R;Hodi, FS;Dranoff, G
通讯作者：
Dranoff, G