Department of Urology, VU University Medical Center, Amsterdam, the Netherlands
Department of Urology, VU University Medical Center, Amsterdam, the Netherlands Department of Internal Medicine, Kennemer Gasthuis Haarlem, the Netherlands.
Anticancer Res. 2014 Jun;34(6):2689-700.
Prophylactic vaccination is arguably the most effective medical preventative method. After local inoculation, vaccines induce antigen-specific systemic immunity, protecting the whole body. Systemic antitumour immunity can cure advanced cancer, but will therapeutic vaccination suffice? A vaccine for castration-refractory prostate cancer (CRPC) was approved by regulatory authority, but its evidence is disputed. We critically reviewed the clinical efficacy of therapeutic cancer vaccines for prostate cancer, including the results of 31 clinical studies employing vaccines-only, and another 10 studies combining vaccines with immune co-stimulation. Vaccinations yielded immunological responses, but no study showed evidence for clinically relevant therapeutic improvement. Clinical failure of therapeutic vaccination is discussed in the light of immunological dogmas and mechanisms of antitumour therapies. We propose that cancer immunotherapy might be improved by immunological danger, i.e. disturbing tumour homeostasis by destroying the tumour tissue or inducing local inflammation. Such danger might override immunological tolerance, and thereby allow clinically relevant anticancer results.
预防性接种可以说是最有效的医学预防方法。局部接种后，疫苗会引起抗原特异性的全身免疫，从而保护全身。全身抗肿瘤免疫可以治愈晚期癌症，但治疗性疫苗是否足够？一种用于去势抵抗性前列腺癌（CRPC）的疫苗已获得监管机构批准，但它的证据存在争议。我们对前列腺癌治疗性癌症疫苗的临床疗效进行了批判性评估，包括仅使用疫苗的 31 项临床研究的结果，以及另外 10 项将疫苗与免疫共刺激联合使用的研究。疫苗接种产生了免疫反应，但没有一项研究显示出具有临床相关治疗改善的证据。根据免疫学教条和抗肿瘤疗法的机制，讨论了治疗性疫苗接种的临床失败。我们提出，通过免疫危险（即通过破坏肿瘤组织或诱导局部炎症来扰乱肿瘤的稳态），癌症免疫疗法可能会得到改善。这种危险可能会克服免疫耐受，从而产生具有临床相关性的抗癌效果。
