個(gè)體化皮膚癌疫苗在臨床試驗(yàn)中顯示有效

個(gè)體化皮膚癌疫苗在臨床試驗(yàn)中顯示有效

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.

一項(xiàng)為期四年的個(gè)體化皮膚癌疫苗一期試驗(yàn)已經(jīng)結(jié)束，表明該疫苗在很長(zhǎng)一段時(shí)間內(nèi)對(duì)抗黑色素瘤有很大的前景。這種疫苗被稱為neoovax，可以刺激免疫系統(tǒng)攻擊高風(fēng)險(xiǎn)致命黑色素瘤患者的腫瘤細(xì)胞。它成功地在所有8名接受治療的患者身上產(chǎn)生了免疫應(yīng)答——他們都在試驗(yàn)期間存活了下來(lái)，其中6人在4年后沒(méi)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.

個(gè)性化癌癥疫苗是對(duì)抗癌癥的最有前途的途徑之一，每年全世界有近1000萬(wàn)人死于癌癥。一種“治愈”所有癌癥的方法，在所有的可能性中，根本不存在——每種癌癥都是遺傳或環(huán)境因素的混合物，呈現(xiàn)出不同的分子，有些療法可能有效，有些則可能無(wú)效。我們最好的反擊可能是個(gè)性化療法或疫苗，它們針對(duì)每個(gè)病人或特定的癌癥類型。

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.

為了制造一種可以對(duì)抗黑色素瘤的疫苗，來(lái)自馬薩諸塞州丹娜-法伯癌癥研究所的科學(xué)家們瞄準(zhǔn)了癌細(xì)胞表面的抗原。這種類型的抗原被稱為新抗原，它發(fā)生了突變，只存在于腫瘤細(xì)胞上——因此，如果免疫系統(tǒng)能夠識(shí)別并攻擊它們，惡性細(xì)胞就能被摧毀。

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包含了這些新抗原的一部分，稱為抗原表位，可以引發(fā)免疫反應(yīng)。然而，這些表位需要為患者量身定制，因此提取患者腫瘤的DNA，分析表位的組成。注射疫苗后，體內(nèi)的t細(xì)胞會(huì)識(shí)別并記住新抗原，希望能阻止黑色素瘤的發(fā)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.

這項(xiàng)研究歷時(shí)4年，追蹤了8名黑色素瘤復(fù)發(fā)幾率很高的患者。接種疫苗四年后，8名患者全部存活，其中6人完全無(wú)病。在血液分析后，研究人員發(fā)現(xiàn)他們的t細(xì)胞對(duì)黑色素瘤新抗原，甚至其他相關(guān)的表位也有反應(yīng)。

“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.

“這些發(fā)現(xiàn)表明，個(gè)人新抗原疫苗可以刺激黑色素瘤患者的持久免疫反應(yīng)，”該研究的共同領(lǐng)導(dǎo)Catherine J. Wu醫(yī)學(xué)博士在一份聲明中說(shuō)，她來(lái)自Dana-Farber、Brigham和婦女醫(yī)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.”

“我們發(fā)現(xiàn)證據(jù)表明，最初的靶向免疫反應(yīng)在過(guò)去幾年里已經(jīng)擴(kuò)大，為患者提供了持續(xù)的預(yù)防疾病的保護(hù)。”

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.

在這8名患者中，有5名患者在試驗(yàn)期間確實(shí)出現(xiàn)了黑色素瘤復(fù)發(fā)，他們接受了手術(shù)或藥物派姆單抗(一種針對(duì)多種癌癥的免疫療法)的治療。其中三名患者現(xiàn)在已經(jīng)痊愈，另外兩名患者的癌細(xì)胞進(jìn)一步擴(kuò)散。他們的研究結(jié)果發(fā)表在《自然》雜志的一篇文章上。

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.

雖然該試驗(yàn)本身就很有希望，但似乎對(duì)抗黑色素瘤最有效的方法將是使用針對(duì)單個(gè)癌癥的多種治療方法。研究人員認(rèn)為，該疫苗在免疫檢查點(diǎn)抑制方面非常有效，這確保了T細(xì)胞能夠摧毀腫瘤細(xì)胞。