Cancer vaccine strategies: translation from mice to human clinical trials.
Cancer vaccine strategies: translation from mice to human clinical trials.
复制标题
DOI：
10.1007/s00262-017-2084-x
复制
发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Wood LV
中科院分区：
文献类型：
--
作者：
Berzofsky JA;Terabe M;Trepel JB;Pastan I;Stroncek DF;Morris JC;Wood LV
We translated 2 cancer vaccine strategies from mice into human clinical trials. 1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells (“epitope enhancement”). In a clinical trial, HLA-A2+ prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with 2 peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs). In stage D0, the Prostate-Specific Antigen (PSA) slope is prognostic of time to radiographic evidence of metastases and death. With no difference between arms, 74% of combined subjects had a decreased PSA slope at 1 year compared to their own baseline slopes (p = 0.0004). For patients vaccinated with DCs, response inversely correlated with a tolerogenic DC signature. A randomized placebo-controlled phase II trial is underway. 2) HER2 is a driver surface oncogene product expressed in multiple tumors. We made an adenoviral vector vaccine expressing the extracellular & transmembrane domains of HER2 and cured mice with large established HER2+ tumors, dependent on antibodies to HER2, not T cells. The mechanism differed from that of trastuzumab. We tested a human version in advanced metastatic cancer patients naïve to HER2-directed therapies. At the 2nd and 3rd dose levels, 45% of evaluable patients showed clinical benefit. Circulating tumor cells also declined in some vaccinated patients. Thus, cancer vaccines developed in mice were successfully translated to humans with promising early results. Both a T-cell epitope-enhanced TARP peptide vaccine in prostate cancer and an anti-HER2 adenoviral antibody-directed vaccine in multiple cancers have been translated from mice to human clinical trials with promising preliminary results.
登录
查看更多内容
影响因子：
56.9
作者：
Morgan, Richard A.;Dudley, Mark E.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
15.9
作者：
Knutson, KL;Schiffman, K;Disis, ML
通讯作者：
Disis, ML
DOI：
10.1073/pnas.94.20.10856
发表时间：
1997-09-30
影响因子：
11.1
作者：
Ahlers, JD;Takeshita, T;Berzofsky, JA
通讯作者：
Berzofsky, JA
影响因子：
6.2
作者：
Holmes, Jarrod P.;Gates, Jeremy D.;Peoples, George E.
通讯作者：
Peoples, George E.
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.