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自体树突状细胞瘤苗治疗非小细胞肺癌的Ⅰ期临床研究。

Phase I study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer.

机构信息

Department of Internal Medicine, Dong-A University College of Medicine, 3-Ga Dongdaeshin-dong, Seo-gu, Busan 602-715, Republic of Korea.

出版信息

Lung Cancer. 2010 Nov;70(2):188-94. doi: 10.1016/j.lungcan.2010.02.006. Epub 2010 Mar 12.

DOI:10.1016/j.lungcan.2010.02.006
PMID:20223553
Abstract

BACKGROUND

A dendritic cell vaccine has been developed as a novel strategy for generating antitumor immunity in the treatment of cancer. The purpose of this study was to assess the maximal tolerated dose, safety, and immunologic response of a new dendritic cell vaccine (DC-Vac) into which tumor lysate was loaded by electroporation and pulse in patients with advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS

Fifteen patients with inoperable stage III or IV NSCLC were assigned to cohorts that received 3, 6, or 12 × 10(6) DC-Vac intradermally 3 times at 2 week intervals. We also evaluated immunologic and tumor responses.

RESULTS

The maximum dose of DC-Vac (12 × 10(6)) was shown to be safe. In 5 of 9 patients, the vaccine resulted in increased interferon (IFN)-γ production by CD8+ cells after exposure to tumor lysate. Additionally, there were mixed responses which do fulfill progressive disease definition but demonstrate some clinical benefit in two patients.

CONCLUSION

The administration of tumor lysate-loaded autologous dendritic cells by electroporation and pulse was non-toxic and induced immunologic responses to tumor antigens. The two mixed tumor responses which were achieved may represent a potential benefit of this new DC-Vac.

摘要

背景

树突状细胞疫苗已被开发为一种治疗癌症的新策略,旨在产生抗肿瘤免疫。本研究旨在评估一种新的树突状细胞疫苗(DC-Vac)的最大耐受剂量、安全性和免疫反应,该疫苗通过电穿孔和脉冲加载肿瘤裂解物,用于治疗晚期非小细胞肺癌(NSCLC)患者。

患者和方法

15 名无法手术的 III 期或 IV 期 NSCLC 患者被分配到接受 3、6 或 12×10^6^ DC-Vac 皮内注射的队列,每 2 周 3 次,共 3 次。我们还评估了免疫和肿瘤反应。

结果

显示 DC-Vac(12×10^6^)的最大剂量是安全的。在 9 名患者中的 5 名中,疫苗接种后,CD8+细胞对肿瘤裂解物产生的干扰素(IFN)-γ增加。此外,有混合反应,符合进展性疾病的定义,但在两名患者中表现出一定的临床获益。

结论

电穿孔和脉冲加载自体树突状细胞的肿瘤裂解物给药无毒性,并诱导针对肿瘤抗原的免疫反应。两种混合肿瘤反应可能代表这种新的 DC-Vac 的潜在益处。

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