Vaccine Clinical Trials

疫苗临床试验

• 批准号: 7338797
• 负责人: James L. Gulley
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7338797
• 关键词: Vaccine; Clinical; Trials

Major scientific achievements include: (a) The completion of the first clinical trials employing an admixture of vectors containing transgenes for a costimulatory molecule and a TAA. Three clinical studies in patients with different stages of prostate cancer demonstrated that vaccine (rV-PSA + rV-B7.1 followed by rF-PSA) could be safely employed with external beam irradiation of tumor, second line hormone therapy, and Taxotere, and provided preliminary evidence of prolongation of time to disease progression, and antigen cascade post-vaccination. (b) The completion of the first clinical trials with rV-, rF-PSA-TRICOM vaccines in patients with metastatic prostate cancer. These studies provided evidence of clinical benefit that correlated with the generation of PSA-specific T-cell responses. These trials have led to planned NCI-sponsored randomized multicenter Phase II and III trials in D0 and D0.5 patients. (c) Completion of the first Phase I/II collaborative clinical trial employing vaccines containing transgenes for three costimulatory molecules (rV-, rF-CEA-TRICOM). This trial demonstrated the advantage of a diversified prime and boost vaccination schema with the inclusion of GM-CSF. Preliminary evidence was seen correlating CEA-specific T-cell responses and survival; this trial also provided evidence for the need for continued boosting with vaccine to maintain disease stabilization. (d) Completion of the first NCI clinical trial employing rV-, rF-PANVAC (CEA-MUC-1-TRICOM) vaccines plus GM-CSF. This trial provided evidence of clinical activity that has led to subsequent clinical trials at NCI and other Cancer Centers. Based on promising hypothesis-driven preclinical results, described in Projects A1-A3, science-based trials have been initiated involving (e) s.c./intratumoral vaccination, in locally advanced prostate cancer, employing i.t. vaccination of rF-PSA-TRICOM plus rF-GM-CSF, (f) CEA-TRICOM vaccination plus external beam irradiation of colon cancer metastatic lesions, (g) vaccine plus anti-CTLA-4 MAb in patients with metastatic prostate cancer, (h) the use of palliative 153Sm-chelate (to alter the phenotype of bone metastases) plus PSA-TRICOM vaccination in prostate cancer patients with bone metastases (in review). (i) The establishment of a network of collaborative clinical trials to provide a scientific-based programmatic approach to cancer vaccine clinical trial development.

主要的科学成就包括：（a）使用含有共刺激分子和TAA转基因的载体混合物完成了第一次临床试验。在不同阶段前列腺癌患者中进行的3项临床研究表明，疫苗（rV-PSA + rV-B7.1，然后是rF-PSA）可以安全地与肿瘤外照射、二线激素治疗和泰索帝联合使用，并提供了延长疾病进展时间和疫苗接种后抗原级联反应的初步证据。(b)在转移性前列腺癌患者中完成rV-、rF-PSA-TRICOM疫苗的首批临床试验。这些研究提供了与PSA特异性T细胞应答的产生相关的临床益处的证据。这些试验已导致计划在D 0和D0.5患者中开展由NCI申办的随机多中心II期和III期试验。(c)使用含有三种共刺激分子（rV-，rF-CEA-TRICOM）转基因的疫苗完成第一个I/II期合作临床试验。该试验证明了包含GM-CSF的多样化初免和加强疫苗接种方案的优势。初步证据表明CEA特异性T细胞应答与存活率相关;该试验还提供了需要继续加强疫苗以维持疾病稳定的证据。(d)完成第一项采用rV-、rF-PANVAC（CEA-MUC-1-TRICOM）疫苗加GM-CSF的NCI临床试验。该试验提供了临床活性的证据，导致NCI和其他癌症中心进行后续临床试验。基于项目A1-A3中描述的有希望的假设驱动的临床前结果，已经启动了基于科学的试验，涉及（e）s.c./肿瘤内接种，在局部晚期前列腺癌中，采用i.t. rF-PSA-TRICOM加rF-GM-CSF的疫苗接种，（f）CEA-TRICOM疫苗接种加结肠癌转移病灶的外部束照射，（g）转移性前列腺癌患者中的疫苗加抗CTLA-4单克隆抗体，（h）具有骨转移的前列腺癌患者中的姑息性153 Sm-螯合物（以改变骨转移的表型）加PSA-TRICOM疫苗接种的使用（综述中）。(i)建立合作临床试验网络，为癌症疫苗临床试验开发提供基于科学的程序化方法。