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转移性黑色素瘤患者的过继性细胞疗法:舍巴医疗中心的临床前开发

Adoptive cell therapy for metastatic melanoma patients: pre-clinical development at the Sheba Medical Center.

作者信息

Besser Michal J, Treves Avraham J, Itzhaki Orit, Hardan Izhar, Nagler Arnon, Papa Moshe Z, Catane Raphael, Winkler Eyal, Shalmon-Zifroni Bruria, Schachter Jacob

机构信息

Ella Institute for Treatment and Research of Melanoma, Sheba Medical Center, Tel Hashomer, Israel.

出版信息

Isr Med Assoc J. 2006 Mar;8(3):164-8.

PMID:16599050
Abstract

BACKGROUND

Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6-10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15-30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

OBJECTIVES

To introduce the TIL technology to advanced metastatic melanoma patients in Israel.

METHODS

We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

RESULTS

TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

CONCLUSIONS

Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

摘要

背景

转移性黑色素瘤是一种侵袭性很强的高度恶性癌症。转移性疾病患者的5年生存率低于5%,中位生存期仅为6至10个月。像达卡巴嗪(DTIC)这样的药物作为单一药物或与其他化疗药物联合使用时,有效率为15%至30%,但缓解期通常较短,对生存期没有影响。基于白细胞介素-2的免疫疗法已显示出更有前景的结果。美国国立卫生研究院最近报告称,淋巴细胞清除化疗后,大量抗肿瘤特异性肿瘤浸润淋巴细胞的过继性转移使51%的患者出现客观缓解。

目的

将肿瘤浸润淋巴细胞(TIL)技术引入以色列的晚期转移性黑色素瘤患者。

方法

我们从肿瘤组织中培养TIL,选择那些对黑色素瘤具有特异性活性的细胞并将其大量扩增。

结果

建立了9例患者的TIL培养物,并检测了它们对患者自体肿瘤细胞的特异性活性。来自5例不同患者的12个TIL培养物显示出预期的抗肿瘤活性,这5例患者成为该治疗的潜在候选者。

结论

在临床实验室环境中成功进行了TIL技术的临床前研究,这种治疗方式已准备好在舍巴医疗中心的埃拉研究所治疗转移性黑色素瘤患者。

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