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I期临床试验:使用负载来自前列腺特异性膜抗原的HLA-A0201特异性肽的自体树突状细胞进行前列腺癌的T细胞治疗。

Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen.

作者信息

Murphy G, Tjoa B, Ragde H, Kenny G, Boynton A

机构信息

Pacific Northwest Cancer Foundation, Cancer Research Division, Northwest Hospital, Seattle, Washington 98125, USA.

出版信息

Prostate. 1996 Dec;29(6):371-80. doi: 10.1002/(SICI)1097-0045(199612)29:6<371::AID-PROS5>3.0.CO;2-B.

DOI:10.1002/(SICI)1097-0045(199612)29:6<371::AID-PROS5>3.0.CO;2-B
PMID:8977634
Abstract

BACKGROUND

Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigations involving the role of T-cell immunity in the clearance of neoplastic cells are now available. Development of T-cell immunotherapy may give a new approach to the treatment of advanced metastatic prostate cancer.

METHODS

A phase I clinical trial assessing the administration of autologous dendritic cells (DC) pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides were conducted. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, respectively).

RESULTS

No significant toxicity was observed in all five groups. Cellular response against PSM-P1 and -P2 was observed in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (groups 4 and 5), respectively. An average decrease in PSA was detected only in group 5. Seven partial responders were identified based on NPCP criteria + PSA.

CONCLUSIONS

Infusions of test substances were well tolerated by all study participants. Detection of cellular response and decrease in PSA level in some patients who received DC pulsed with PSM-P2 indicate this method's potential in prostate cancer therapy.

摘要

背景

转移性前列腺癌的传统治疗方法未能在所有患者中展现出治愈潜力。目前已有关于T细胞免疫在清除肿瘤细胞中作用的研究。T细胞免疫疗法的发展可能为晚期转移性前列腺癌的治疗提供一种新方法。

方法

进行了一项I期临床试验,评估用HLA - A0201特异性前列腺特异性膜抗原(PSMA)肽脉冲处理的自体树突状细胞(DC)的给药情况。参与者被分为五组,分别接受单独的四次或五次肽输注(PSM - P1或PSM - P2;分别为第1组和第2组)、自体DC(第3组)或用PSM - P1或P2脉冲处理的DC(分别为第4组和第5组)。

结果

所有五组均未观察到明显毒性。在分别接受用PSM - P1或 - P2脉冲处理的DC输注的HLA - A2 +患者(第4组和第5组)中观察到针对PSM - P1和 - P2的细胞反应。仅在第5组检测到PSA平均下降。根据NPCP标准 + PSA确定了7名部分缓解者。

结论

所有研究参与者对受试物质的输注耐受性良好。在一些接受用PSM - P2脉冲处理的DC的患者中检测到细胞反应和PSA水平下降,表明该方法在前列腺癌治疗中的潜力。

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