个体化皮肤癌疫苗在临床试验中显示有效

个体化皮肤癌疫苗在临床试验中显示有效

A four-year-long Phase 1 trial of a personalized skin cancer vaccine has concluded and shows that the vaccine has huge promise in fighting off melanoma over a long period of time. The vaccine, called NeoVax, stimulates the immune system to attack tumor cells in patients with high-risk deadly melanoma. It was successful in bringing about an immune response in all eight patients who received it – all of which survived the trial period, and six of which were disease-free after four years.

一项为期四年的个体化皮肤癌疫苗一期试验已经结束，表明该疫苗在很长一段时间内对抗黑色素瘤有很大的前景。这种疫苗被称为neoovax，可以刺激免疫系统攻击高风险致命黑色素瘤患者的肿瘤细胞。它成功地在所有8名接受治疗的患者身上产生了免疫应答——他们都在试验期间存活了下来，其中6人在4年后没有疾病。

Personalized cancer vaccines are one of the most promising avenues for battling cancers that take almost 10 million lives each year worldwide. One "cure" for all cancers, in all likelihood, simply doesn’t exist – each cancer is its own cocktail of genetic or environmental factors, presenting different molecules that some therapies may be effective against and some may not. Our best chance at fighting back is most likely personalized therapies or vaccines, which are specifically made for each patient or exact cancer type.

个性化癌症疫苗是对抗癌症的最有前途的途径之一，每年全世界有近1000万人死于癌症。一种“治愈”所有癌症的方法，在所有的可能性中，根本不存在——每种癌症都是遗传或环境因素的混合物，呈现出不同的分子，有些疗法可能有效，有些则可能无效。我们最好的反击可能是个性化疗法或疫苗，它们针对每个病人或特定的癌症类型。

To make a vaccine that could combat melanoma, scientists from the Dana-Farber Cancer Institute, Massachusetts, aimed to target antigens that present on the surface of cancer cells. This type of antigen, called a neoantigen, is mutated and only exists on tumor cells – so if the immune system could be taught to recognize and attack them, the malignant cells could be destroyed.

为了制造一种可以对抗黑色素瘤的疫苗，来自马萨诸塞州丹娜-法伯癌症研究所的科学家们瞄准了癌细胞表面的抗原。这种类型的抗原被称为新抗原，它发生了突变，只存在于肿瘤细胞上——因此，如果免疫系统能够识别并攻击它们，恶性细胞就能被摧毁。

Jack Dunhill

NeoVax contains parts of these neoantigens, called epitopes, that initiate an immune response. However, these epitopes need to be tailor-made to the patient, so DNA is extracted for the patient’s tumor and analyzed for the makeup of the epitopes. When the vaccine is injected, T-cells within the body will recognize the neoantigens and remember them, hopefully preventing melanoma development.

NeoVax包含了这些新抗原的一部分，称为抗原表位，可以引发免疫反应。然而，这些表位需要为患者量身定制，因此提取患者肿瘤的DNA，分析表位的组成。注射疫苗后，体内的t细胞会识别并记住新抗原，希望能阻止黑色素瘤的发展。

The study spanned four years, following eight patients with a high chance of melanoma recurrence. Four years after vaccination, all eight patients were alive, with six being completely disease-free. After blood analysis, the researchers discovered their T-cells were responding to melanoma neoantigens, and even other related epitopes as well.

这项研究历时4年，追踪了8名黑色素瘤复发几率很高的患者。接种疫苗四年后，8名患者全部存活，其中6人完全无病。在血液分析后，研究人员发现他们的t细胞对黑色素瘤新抗原，甚至其他相关的表位也有反应。

“These findings demonstrate that a personal neoantigen vaccine can stimulate a durable immune response in patients with melanoma,” says study co-leader Catherine J. Wu, MD, of Dana-Farber, Brigham and Women’s Hospital (BWH), and the Broad Institute, in a statement.

“这些发现表明，个人新抗原疫苗可以刺激黑色素瘤患者的持久免疫反应，”该研究的共同领导Catherine J. Wu医学博士在一份声明中说，她来自Dana-Farber、Brigham和妇女医院(BWH)以及Broad研究所。

“We found evidence that the initial, targeted immune response has broadened over the years to provide patients with continued protection from the disease.”

“我们发现证据表明，最初的靶向免疫反应在过去几年里已经扩大，为患者提供了持续的预防疾病的保护。”

Of the eight, five patients did see a recurrence of melanoma during the trial which was treated with either surgery or the drug pembrolizumab, an immunotherapy treatment against a variety of cancers. Three of these patients are now disease-free, whilst two saw the cancer spread further. Their results were published in an article to Nature.

在这8名患者中，有5名患者在试验期间确实出现了黑色素瘤复发，他们接受了手术或药物派姆单抗(一种针对多种癌症的免疫疗法)的治疗。其中三名患者现在已经痊愈，另外两名患者的癌细胞进一步扩散。他们的研究结果发表在《自然》杂志的一篇文章上。

Whilst the trial is promising on its own, it appears the most effective method of combatting melanoma will be utilizing the vaccine in a multi-treatment approach, tailored to individual cancers. The researchers suggest the vaccine works extremely well with immune checkpoint inhibition, which ensures T-cells can destroy tumor cells.

虽然该试验本身就很有希望，但似乎对抗黑色素瘤最有效的方法将是使用针对单个癌症的多种治疗方法。研究人员认为，该疫苗在免疫检查点抑制方面非常有效，这确保了T细胞能够摧毁肿瘤细胞。