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定制式疫苗為胰腺癌治療帶來新突破

BETH GREENFIELD
2025-03-04

一款mRNA疫苗的小型臨床試驗給胰腺癌患帶來了福音。

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胰腺癌是死亡率最高的癌癥之一,。圖片來源:GETTY IMAGES

胰腺癌是致死率最高的癌癥之一,其確診患者的死亡率高達88%,,五年以上生存率不超過13%,,手術后7-9個月的復發(fā)率接近90%。美國的胰腺癌死亡率亦處于上升趨勢,。

不過,,一款mRNA胰腺癌疫苗的小型臨床試驗頗有希望的結果帶來了新的曙光。

維諾德·巴拉錢德蘭博士在斯隆—凱特林癌癥研究所(MSK)的一則新聞稿中表示:“新出爐的一期實驗數(shù)據(jù)十分喜人,。數(shù)據(jù)顯示,,這款試驗治療性mRNA疫苗有望在接種數(shù)年之后激活能夠把胰腺癌識別為異物的抗腫瘤T細胞?!痹撗芯坑伤孤 獎P特林癌癥研究所旗下奧拉揚癌癥疫苗中心(OCCV)主導,。

該實驗測試了一款名為autogene cevumeran的治療性mRNA癌癥疫苗,其設計初衷是通過提供癌癥中發(fā)現(xiàn)的蛋白(腫瘤抗原),,來訓練免疫系統(tǒng),,讓其將癌細胞識別為異物,繼而治療不是預防癌癥,。實驗結果已于今年2月初發(fā)表于《自然》(Nature)期刊,。

一個由16名斯隆—凱特林癌癥研究所病患組成的小組接受了根據(jù)其腫瘤特征定制的疫苗,同時還服用了一款名為阿特珠單抗的藥物,,并接受了mFOLFIRINOX化療方案的治療,。這些病患此前均已摘除了腫瘤。

初步結果顯示,,該疫苗未產生嚴重副作用,,2023年的《自然》期刊文章也提到了這一點。

半數(shù)病患出現(xiàn)了免疫應答,。在這8名患者中,,僅有兩名在隨后的三年內出現(xiàn)了癌癥復發(fā),,而在無應答的其他8名患者中,有7名出現(xiàn)了復發(fā),。研究人員并不能確認是疫苗導致了復發(fā)的延遲,。

有一名參與者在不到兩年的時間內去世。

最新發(fā)現(xiàn)顯示,,在患者接受了近4年的治療之后,,研究人員檢測到了大量疫苗激發(fā)的T細胞(源于骨髓中的干細胞,而骨髓是免疫系統(tǒng)的組件之一),。

即便患者在疫苗接種后接受化療時,,這些T細胞亦保留了其抗癌特性。研究人員此前認為化療可能會削弱疫苗的效果,,但并未出現(xiàn)這一現(xiàn)象,。

這些發(fā)現(xiàn)為使用類似定制式mRNA療法來治療一系列癌癥帶來了希望。

兼任奧拉揚癌癥疫苗中心主任的巴拉錢德蘭表示:“對于胰腺癌患者而言,,我們最新的結果再次顯示,,使用定制mRNA疫苗靶向治療每位病患腫瘤的方式是可行的。如果這種療法對于胰腺癌奏效,,那么理論上就可以為其他癌癥開發(fā)治療性疫苗,。”

該實驗贊助商基因泰克公司(Genentech)和BioNtech公司又贊助了二期臨床實驗,,后者已于去年7月啟動,,以評估疫苗對更大范圍病患群體的療效。二期實驗在全球多個地區(qū)共招募了約260名病患,。

巴拉錢德蘭表示:“按照病患個人量身定制一款癌癥疫苗十分復雜,,因為癌癥源于病患自身細胞,因此與甄別病毒這類外來病原的蛋白相比,,免疫系統(tǒng)甄別癌細胞蛋白的難度更大,。不過,借助癌癥生物學的進步,、新生物科技的發(fā)展以及基因測序,,人們如今已經能夠設計檢測性疫苗,后者有望幫助免疫系統(tǒng)區(qū)分上述蛋白,?!保ㄘ敻恢形木W(wǎng))

譯者:馮豐

審校:夏林

胰腺癌是致死率最高的癌癥之一,其確診患者的死亡率高達88%,,五年以上生存率不超過13%,,手術后7-9個月的復發(fā)率接近90%。美國的胰腺癌死亡率亦處于上升趨勢。

不過,,一款mRNA胰腺癌疫苗的小型臨床試驗頗有希望的結果帶來了新的曙光。

維諾德·巴拉錢德蘭博士在斯隆—凱特林癌癥研究所(MSK)的一則新聞稿中表示:“新出爐的一期實驗數(shù)據(jù)十分喜人,。數(shù)據(jù)顯示,,這款試驗治療性mRNA疫苗有望在接種數(shù)年之后激活能夠把胰腺癌識別為異物的抗腫瘤T細胞?!痹撗芯坑伤孤 獎P特林癌癥研究所旗下奧拉揚癌癥疫苗中心(OCCV)主導,。

該實驗測試了一款名為autogene cevumeran的治療性mRNA癌癥疫苗,其設計初衷是通過提供癌癥中發(fā)現(xiàn)的蛋白(腫瘤抗原),,來訓練免疫系統(tǒng),,讓其將癌細胞識別為異物,繼而治療不是預防癌癥,。實驗結果已于本月初發(fā)表于《自然》(Nature)期刊,。

一個由16名斯隆—凱特林癌癥研究所病患組成的小組接受了根據(jù)其腫瘤特征定制的疫苗,同時還服用了一款名為阿特珠單抗的藥物,,并接受了mFOLFIRINOX化療方案的治療,。這些病患此前均已摘除了腫瘤。

初步結果顯示,,該疫苗未產生嚴重副作用,,2023年的《自然》期刊文章也提到了這一點。

半數(shù)病患出現(xiàn)了免疫應答,。在這8名患者中,,僅有兩名在隨后的三年內出現(xiàn)了癌癥復發(fā),而在無應答的其他8名患者中,,有7名出現(xiàn)了復發(fā),。研究人員并不能確認是疫苗導致了復發(fā)的延遲。

有一名參與者在不到兩年的時間內去世,。

最新發(fā)現(xiàn)顯示,,在患者接受了近4年的治療之后,研究人員檢測到了大量疫苗激發(fā)的T細胞(源于骨髓中的干細胞,,而骨髓是免疫系統(tǒng)的組件之一),。

即便患者在疫苗接種后接受化療時,這些T細胞亦保留了其抗癌特性,。研究人員此前認為化療可能會削弱疫苗的效果,,但并未出現(xiàn)這一現(xiàn)象。

這些發(fā)現(xiàn)為使用類似定制式mRNA療法來治療一系列癌癥帶來了希望,。

兼任奧拉揚癌癥疫苗中心主任的巴拉錢德蘭表示:“對于胰腺癌患者而言,,我們最新的結果再次顯示,使用定制mRNA疫苗靶向治療每位病患腫瘤的方式是可行的。如果這種療法對于胰腺癌奏效,,那么理論上就可以為其他癌癥開發(fā)治療性疫苗,。”

該實驗贊助商基因泰克公司(Genentech)和BioNtech公司又贊助了二期臨床實驗,,后者已于去年7月啟動,,以評估疫苗對更大范圍病患群體的療效。二期實驗在全球多個地區(qū)共招募了約260名病患,。

巴拉錢德蘭表示:“按照病患個人量身定制一款癌癥疫苗十分復雜,,因為癌癥源于病患自身細胞,因此與甄別病毒這類外來病原的蛋白相比,,免疫系統(tǒng)甄別癌細胞蛋白的難度更大,。不過,借助癌癥生物學的進步,、新生物科技的發(fā)展以及基因測序,,人們如今已經能夠設計檢測性疫苗,后者有望幫助免疫系統(tǒng)區(qū)分上述蛋白,?!保ㄘ敻恢形木W(wǎng))

譯者:馮豐

審校:夏林

Pancreatic cancer is one of the deadliest types of cancer, with fewer than 13% of people diagnosed with it surviving for more than five years. It kills 88% of its patients, and its recurrence rate, after surgery, is nearly 90% within seven to nine months. U.S. mortality rates, meanwhile, are on the upswing.

But promising results from a small clinical trial for an mRNA pancreatic cancer vaccine are fueling new rays of hope.

“The latest data from the Phase I trial are encouraging,” said lead author Dr. Vinod Balachandran in a news release from Memorial Sloan Kettering (MSK), home to the Olayan Center for Cancer Vaccines (OCCV), the research hub behind the study. “They suggest this investigational therapeutic mRNA vaccine can mobilize anti-tumor T cells that may recognize pancreatic cancers as foreign, potentially years after vaccination.”

The trial, which had its results published earlier this month in the journal Nature, tested a therapeutic mRNA cancer vaccine called autogene cevumeran; it’s designed to treat, not prevent, cancer by delivering proteins found in cancer (neoantigens) as a way to train the immune system to recognize cancer cells as foreign.

A small group of 16 MSK patients, each of whom had had tumors removed, received personalized versions of the vaccine, based on the specifics of their tumor; they also received an immunotherapy drug called atezolizumab and a chemotherapy regimen called mFOLFIRINOX.

There were no reports of serious side effects—something that showed in early results and was noted in a 2023 Nature article.

Half of patients saw an immune response. Of those eight, just two had their cancer return during the three-year follow-up—compared with seven of the eight who did not respond to the vaccine. Researchers are not yet certain that the vaccine caused the delay in recurrence.

One participant died within two years.

In these latest findings, researchers could detect substantial vaccine-stimulated T cells (which are developed from stem cells in bone marrow as part of the immune system) up to nearly four years after treatment.

Those T cells retained their anti-cancer activity even after patients received post-vaccine chemotherapy—something that researchers thought could diminish the vaccine’s effects but did not.

The findings hold promise for treating a range of cancers with the same personalized mRNA approach.

“For patients with pancreatic cancer, our latest results continue to support the approach of using personalized mRNA vaccines to target neoantigens in each patient’s tumor,” Balachandran, also director of the OCCV, said. “If you can do this in pancreas cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types.”

Genentech and BioNTech, sponsors of the trial, are behind a Phase II clinical trial that began in July to evaluate the vaccine in a larger patient group, enrolling approximately 260 patients at various sites around the world.

“Designing a cancer vaccine tailored to an individual is complex,” said Balachandran. “Because cancers arise from our own cells, it is much harder for the immune system to distinguish proteins in cancer cells as foreign compared with proteins in pathogens like viruses. But important advances in cancer biology, the development of novel biotechnologies, and genomic sequencing now make it possible to design investigational vaccines that may help the immune system to tell the difference.”

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