"It is the antigen(s), stupid" and other lessons from over a decade of vaccitherapy of human cancer.
"It is the antigen(s), stupid" and other lessons from over a decade of vaccitherapy of human cancer.
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DOI：
10.1016/j.smim.2008.07.003
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发表时间：
2008-10
影响因子：
7.8
通讯作者：
Srivastava PK
中科院分区：
文献类型：
--
作者：
Buckwalter MR;Srivastava PK
经验教训是：（a）人类癌症肯定会对免疫操纵作出反应。因此，人类癌症免疫治疗的努力是值得的。(b)预防与治疗既存疾病有很大的不同，因此不应从成功的预防研究中获得太多的热情。即使在常规实现了稳健预防的感染原的情况下，一旦疾病确立，治疗几乎是不可能的。(c)使用适当的小鼠和大鼠癌症模型进行研究是有用的。那些从未通过免疫疗法治愈过小鼠癌症的人通常最有信心地提出了在小鼠中治愈癌症很容易的概念。(d)对詹姆斯·卡维尔点点头，这是抗原，傻瓜！我们仍然不知道保护性肿瘤抗原的身份。如果可以从中吸取任何教训，那么很可能是癌症免疫治疗必须摆脱化疗的一刀切的治疗模式，必须转向个性化的方法。(e)所有目标都是平等的，但有些目标比其他目标更平等。关键是对癌症的特异性。这并不一定意味着对癌细胞的特异性。(f)最好是在最小残留病的情况下尝试疫苗治疗，即使这肯定是耗时和昂贵的。在大体积疾病的情况下，疫苗治疗必须与抑制信号的阻断或下调T细胞的耗竭相结合。抑制效应子水平是抑制免疫应答的关键。单独的疫苗疗法或单独的免疫调节不太可能成功治疗巨大转移性疾病。
The lessons are: (a) Human cancers certainly respond to immunological manipulations. Efforts at human cancer immunotherapy are therefore worthwhile. (b) Prophylaxis is very different from therapy of pre-existing disease, and hence much enthusiasm should not be derived from successful prophylaxis studies. Even in case of infectious agents against which robust prophylaxis is routinely achieved, therapy is nearly impossible once the disease has established. (c) Studies with appropriate cancer models of mice and rats are useful. The notion that it is easy to cure cancers in mice is generally advanced the most confidently by those who have never cured a mouse of cancer by immunotherapy. (d) With a nod to James Carville, it is the antigen(s), stupid! We still do not know the identity of protective tumor antigens. If any lesson can be drawn at all, it may well be that cancer immunotherapy must move away from the one-shoe-fits-all therapeutic models of chemotherapy and must move to individualized approaches. (e) All targets are equal, but some are more equal than others. The key is specificity for cancer. That does not necessarily mean specificity for cancer cells. (f) Vaccitherapy must be attempted preferably in the minimal residual disease setting, even though this is certain to be time-taking and expensive. In the setting of bulky disease, vaccitherapy must be combined with blockade of inhibitory signals, or depletion of down-regulatory T cells. Inhibition of effector level suppression of immune response is a key. Vaccitherapy alone or immuno-modulation alone is unlikely to succeed in therapy of bulky metastatic disease.
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影响因子：
158.5
作者：
Gogas, H;Ioannovich, J;Kirkwood, JM
通讯作者：
Kirkwood, JM
DOI：
10.1084/jem.185.4.695
发表时间：
1997-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dubey P;Hendrickson RC;Meredith SC;Siegel CT;Shabanowitz J;Skipper JC;Engelhard VH;Hunt DF;Schreiber H
通讯作者：
Schreiber H
影响因子：
5.4
作者：
Heckman, Karin L.;Schenk, Erin L.;Pease, Larry R.
通讯作者：
Pease, Larry R.
影响因子：
4.8
作者：
Binder, RJ;Blachere, NE;Srivastava, PK
通讯作者：
Srivastava, PK
DOI：
10.1073/pnas.0500090102
发表时间：
2005-11-01
影响因子：
11.1
作者：
Lennerz, V;Fatho, M;Wölfel, T
通讯作者：
Wölfel, T