Vaccine Clinical Trials

主要的科学成就包括：(a)完成了第一次临床试验，使用含有共刺激分子和TAA的转基因载体的混合物。三项不同分期前列腺癌患者的临床研究表明，疫苗（rV-PSA + rV-B7.1后rF-PSA）可安全用于肿瘤外束照射、二线激素治疗和泰索帝，并提供了疫苗接种后疾病进展时间延长和抗原级联的初步证据。(b)在转移性前列腺癌患者中完成了rV-、rF-PSA-TRICOM疫苗的首次临床试验。这些研究提供了与psa特异性t细胞反应产生相关的临床益处的证据。这些试验导致nci计划在D0和D0.5患者中进行随机多中心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阶段/第二阶段合作临床试验。该试验证明了包含GM-CSF的多样化初始和强化疫苗接种方案的优势。初步证据表明cea特异性t细胞反应与生存相关；该试验还提供了证据，证明需要继续加强疫苗接种以维持疾病稳定。(d)完成首个采用rV-、rF-PANVAC （CEA-MUC-1-TRICOM）疫苗加GM-CSF的NCI临床试验。该试验为NCI和其他癌症中心后续的临床试验提供了临床活性的证据。基于A1-A3项目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，包括(e) s.c c /肿瘤内疫苗接种，局部晚期前列腺癌，采用rF-PSA-TRICOM疫苗接种加rF-GM-CSF， (f) CEA-TRICOM疫苗接种加结肠癌转移灶的外部束照射，(g)转移性前列腺癌患者的疫苗加抗ctla -4 MAb。(h)在骨转移的前列腺癌患者中使用姑息性153sm -螯合剂（改变骨转移的表型）加PSA-TRICOM疫苗（回顾中）。(i)建立协作临床试验网络，为癌症疫苗临床试验发展提供以科学为基础的方案方法。

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.