胰腺癌是致死率最高的癌症之一,其确诊患者的死亡率高达88%,五年以上生存率不超过13%,手术后7-9个月的复发率接近90%。美国的胰腺癌死亡率亦处于上升趋势。
不过,一款mRNA胰腺癌疫苗的小型临床试验颇有希望的结果带来了新的曙光。
维诺德·巴拉钱德兰博士在斯隆—凯特林癌症研究所(MSK)的一则新闻稿中表示:“新出炉的一期实验数据十分喜人。数据显示,这款试验治疗性mRNA疫苗有望在接种数年之后激活能够把胰腺癌识别为异物的抗肿瘤T细胞。”该研究由斯隆—凯特林癌症研究所旗下奥拉扬癌症疫苗中心(OCCV)主导。
该实验测试了一款名为autogene cevumeran的治疗性mRNA癌症疫苗,其设计初衷是通过提供癌症中发现的蛋白(肿瘤抗原),来训练免疫系统,让其将癌细胞识别为异物,继而治疗不是预防癌症。实验结果已于今年2月初发表于《自然》(Nature)期刊。
一个由16名斯隆—凯特林癌症研究所病患组成的小组接受了根据其肿瘤特征定制的疫苗,同时还服用了一款名为阿特珠单抗的药物,并接受了mFOLFIRINOX化疗方案的治疗。这些病患此前均已摘除了肿瘤。
初步结果显示,该疫苗未产生严重副作用,2023年的《自然》期刊文章也提到了这一点。
半数病患出现了免疫应答。在这8名患者中,仅有两名在随后的三年内出现了癌症复发,而在无应答的其他8名患者中,有7名出现了复发。研究人员并不能确认是疫苗导致了复发的延迟。
有一名参与者在不到两年的时间内去世。
最新发现显示,在患者接受了近4年的治疗之后,研究人员检测到了大量疫苗激发的T细胞(源于骨髓中的干细胞,而骨髓是免疫系统的组件之一)。
即便患者在疫苗接种后接受化疗时,这些T细胞亦保留了其抗癌特性。研究人员此前认为化疗可能会削弱疫苗的效果,但并未出现这一现象。
这些发现为使用类似定制式mRNA疗法来治疗一系列癌症带来了希望。
兼任奥拉扬癌症疫苗中心主任的巴拉钱德兰表示:“对于胰腺癌患者而言,我们最新的结果再次显示,使用定制mRNA疫苗靶向治疗每位病患肿瘤的方式是可行的。如果这种疗法对于胰腺癌奏效,那么理论上就可以为其他癌症开发治疗性疫苗。”
该实验赞助商基因泰克公司(Genentech)和BioNtech公司又赞助了二期临床实验,后者已于去年7月启动,以评估疫苗对更大范围病患群体的疗效。二期实验在全球多个地区共招募了约260名病患。
巴拉钱德兰表示:“按照病患个人量身定制一款癌症疫苗十分复杂,因为癌症源于病患自身细胞,因此与甄别病毒这类外来病原的蛋白相比,免疫系统甄别癌细胞蛋白的难度更大。不过,借助癌症生物学的进步、新生物科技的发展以及基因测序,人们如今已经能够设计检测性疫苗,后者有望帮助免疫系统区分上述蛋白。”(财富中文网)
译者:冯丰
审校:夏林
胰腺癌是致死率最高的癌症之一,其确诊患者的死亡率高达88%,五年以上生存率不超过13%,手术后7-9个月的复发率接近90%。美国的胰腺癌死亡率亦处于上升趋势。
不过,一款mRNA胰腺癌疫苗的小型临床试验颇有希望的结果带来了新的曙光。
维诺德·巴拉钱德兰博士在斯隆—凯特林癌症研究所(MSK)的一则新闻稿中表示:“新出炉的一期实验数据十分喜人。数据显示,这款试验治疗性mRNA疫苗有望在接种数年之后激活能够把胰腺癌识别为异物的抗肿瘤T细胞。”该研究由斯隆—凯特林癌症研究所旗下奥拉扬癌症疫苗中心(OCCV)主导。
该实验测试了一款名为autogene cevumeran的治疗性mRNA癌症疫苗,其设计初衷是通过提供癌症中发现的蛋白(肿瘤抗原),来训练免疫系统,让其将癌细胞识别为异物,继而治疗不是预防癌症。实验结果已于本月初发表于《自然》(Nature)期刊。
一个由16名斯隆—凯特林癌症研究所病患组成的小组接受了根据其肿瘤特征定制的疫苗,同时还服用了一款名为阿特珠单抗的药物,并接受了mFOLFIRINOX化疗方案的治疗。这些病患此前均已摘除了肿瘤。
初步结果显示,该疫苗未产生严重副作用,2023年的《自然》期刊文章也提到了这一点。
半数病患出现了免疫应答。在这8名患者中,仅有两名在随后的三年内出现了癌症复发,而在无应答的其他8名患者中,有7名出现了复发。研究人员并不能确认是疫苗导致了复发的延迟。
有一名参与者在不到两年的时间内去世。
最新发现显示,在患者接受了近4年的治疗之后,研究人员检测到了大量疫苗激发的T细胞(源于骨髓中的干细胞,而骨髓是免疫系统的组件之一)。
即便患者在疫苗接种后接受化疗时,这些T细胞亦保留了其抗癌特性。研究人员此前认为化疗可能会削弱疫苗的效果,但并未出现这一现象。
这些发现为使用类似定制式mRNA疗法来治疗一系列癌症带来了希望。
兼任奥拉扬癌症疫苗中心主任的巴拉钱德兰表示:“对于胰腺癌患者而言,我们最新的结果再次显示,使用定制mRNA疫苗靶向治疗每位病患肿瘤的方式是可行的。如果这种疗法对于胰腺癌奏效,那么理论上就可以为其他癌症开发治疗性疫苗。”
该实验赞助商基因泰克公司(Genentech)和BioNtech公司又赞助了二期临床实验,后者已于去年7月启动,以评估疫苗对更大范围病患群体的疗效。二期实验在全球多个地区共招募了约260名病患。
巴拉钱德兰表示:“按照病患个人量身定制一款癌症疫苗十分复杂,因为癌症源于病患自身细胞,因此与甄别病毒这类外来病原的蛋白相比,免疫系统甄别癌细胞蛋白的难度更大。不过,借助癌症生物学的进步、新生物科技的发展以及基因测序,人们如今已经能够设计检测性疫苗,后者有望帮助免疫系统区分上述蛋白。”(财富中文网)
译者:冯丰
审校: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.”