近日,匹茲堡大學癌癥研究院的科學家研發出一種針對結腸癌的疫苗,能在高危人群出現結腸癌早期跡象時啟動人體的免疫功能對其進行攻擊。
由匹茲堡大學研發的這種疫苗是該領域首款被用于人體檢測的疫苗。前臨床模型試驗顯示,這種疫苗可靶向作用于腫瘤內的異常細胞,從而發揮相關的治療作用。該疫苗可靶向作用于一種特定的細胞蛋白,這種蛋白在腫瘤發生惡化以及腺瘤(一種前癌腫瘤)出現之前發生改變并過量生成。這種蛋白會在胰腺癌、乳腺癌、肺癌和前列腺癌中出現異常。匹茲堡大學研究人員計劃就這種疫苗對這些癌癥的有效性進行檢測。
在之前的一項小型臨床檢測中,研究人員對39名年齡在40到70歲之間的患者進行了這種疫苗的檢測,這些患者雖然沒有癌癥,但卻有晚期腺癌病史。結果顯示,疫苗對其中的17名(44%)患者起到了明顯的效果。
疫苗研發者、匹茲堡大學醫學院免疫科主任Olivera Finn表示:“這種預防結腸癌的疫苗可增強人體的自然免疫監控功能,從而或能在前癌病變發展到腫瘤之前對其進行清除。這樣就能避免因重復進行侵入性監控檢測(例如結腸鏡檢查,這種檢查目前常被用于發現并移除前癌息肉)而給患者帶來的相關風險和不便。”
臨床試驗中,患者一開始會接受一定劑量的疫苗注射,而在之后2周和10周的時候再分別接種一次。研究人員在接種前和接種后12周、28周以及1年的時候分別提取患者的血液樣本,對患者的免疫反應進行評估。患者在1年之后需要再進行一次強化注射以保證免疫反應的持續有效性。
MUC1 Vaccine for Individuals with Advanced Adenoma of the Colon: A Cancer Immunoprevention Feasibility Study
Abstract
Cancer vaccines based on human tumor-associated antigens (TAA) have been tested in patients with advanced or recurrent cancer, in combination with or following standard therapy. Their immunogenicity and therapeutic efficacy has been difficult to properly evaluate in that setting characterized by multiple highly suppressive effects of the tumor and the standard therapy on the patient's immune system. In animal models of human cancer, vaccines administered in the prophylactic setting are most immunogenic and effectively prevent cancer development and progression. We report results of a clinical study that show that in patients without cancer but with a history of premalignant lesions (advanced colonic adenomas, precursors to colon cancer), a vaccine based on the TAA MUC1 was highly immunogenic in 17 of 39 (43.6%) of vaccinated individuals, eliciting high levels of anti-MUC1 immunoglobulin G (IgG) and long-lasting immune memory. Lack of response in 22 of 39 individuals was correlated with high levels of circulating myeloid-derived suppressor cells (MDSC) prevaccination. Vaccine-elicited MUC1-specific immune response and immune memory were not associated with significant toxicity. Our study shows that vaccines based on human TAAs are immunogenic and safe and capable of eliciting long-term memory that is important for cancer prevention. We also show that in the premalignant setting, immunosuppressive environment (e.g., high levels of MDSC) might already exist in some individuals, suggesting an even earlier premalignant stage or preselection of nonimmunosuppressed patients for prophylactic vaccination.
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