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针对前列腺癌的载 PSMA 自体树突状细胞疫苗:DCvax 的变革性未来。

A changing world for DCvax: a PSMA loaded autologous dendritic cell vaccine for prostate cancer.

机构信息

Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL 33612, USA.

出版信息

Expert Opin Biol Ther. 2009 Dec;9(12):1565-75. doi: 10.1517/14712590903446921.

Abstract

BACKGROUND

Northwest Therapeutics' DCvax-prostate consists of autologous dendritic cells (DCs) loaded with prostate-specific membrane antigen (PSMA) peptides, administered intravenously. Phase I-II testing, a decade ago, showed clinical benefit and immunological response in some patients. More recently DCvax brain, a product using a similar DC platform showed encouraging Phase I-II results and sipleucel-T, a prostatic acid phosphatase (PAP)-directed DC immunotherapy had positive Phase III results.

OBJECTIVE

Features of the clinical setting into which a new immunotherapy could be introduced are discussed, to refine a perspective on DCvax-prostate in the context of evolving prostate cancer therapeutics. PSMA-directed therapeutics and immune anticancer technologies are reviewed, and the clinical and immunological correlative testing of DCvax-prostate is discussed.

METHODS

Clinical and preclinical data from peer-reviewed literature, meetings proceedings and manufacturer-provided information are considered.

CONCLUSION

DCvax-prostate had encouraging early-phase trial results, but development and testing had stalled. As a more detailed understanding of patient-selection for capacity for anticancer immune response, the quantitation of immunological correlates, and the changing marketplace develop, it is appealing to consider a well tolerated, PSMA-directed autologous dendritic cell therapeutic product. Further clinical trial development of DCvax-prostate is warranted, and required if it is to find a relevant clinical application.

摘要

背景

西北治疗公司的 DCvax-prostate 由负载有前列腺特异性膜抗原(PSMA)肽的自体树突状细胞(DC)组成,通过静脉注射给药。十年前的 I- II 期测试显示,一些患者具有临床获益和免疫反应。最近,使用类似 DC 平台的 DCvax 脑产品显示出令人鼓舞的 I- II 期结果,而针对前列腺酸性磷酸酶(PAP)的 DC 免疫疗法 simpleucel-T 则取得了积极的 III 期结果。

目的

讨论新免疫疗法引入临床环境的特点,以在不断发展的前列腺癌治疗背景下细化对 DCvax-prostate 的观点。回顾了 PSMA 导向疗法和免疫抗癌技术,并讨论了 DCvax-prostate 的临床和免疫相关性检测。

方法

考虑了同行评议文献、会议记录和制造商提供的信息中的临床和临床前数据。

结论

DCvax-prostate 在早期试验中取得了令人鼓舞的结果,但开发和测试已经停滞不前。随着对患者选择抗癌免疫反应能力的更详细了解、免疫相关性的定量以及不断变化的市场的发展,考虑使用耐受性良好、PSMA 导向的自体树突状细胞治疗产品是很有吸引力的。需要进一步开发 DCvax-prostate 的临床试验,如果要找到相关的临床应用,则需要进行临床试验。

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