製備用於開發癌症疫苗之異元二價醣抗原

Abstract

大部分的癌症細胞表面會表現多量的特定醣抗原，先前研究顯示出Globo H, SSEA-4, SSEA-3等三種醣抗原會大量表現在至少16種不同類型的癌症細胞表面上而且在正常細胞中未被發現。此三種醣抗原之任一種在這16種癌症細胞中，出現的比例高達70%以上。因此，Globo H, SSEA-4, SSEA-3適合並有潛力做為抗癌疫苗之候選物。目前的臨床研究大多都是針對單一抗原所發展出來的疫苗，雖然本實驗室先前研發出的Globo H-DT疫苗可同時誘發針對Globo H, SSEA-3及SSEA-4此三種醣抗原之抗體，但其主要還是針對Globo H及SSEA-3的醣抗原。因此，在本篇研究中，我們想設計出一個多價的治療型抗癌疫苗，使其誘發出的抗體能夠對此三種醣抗原都具有高度的結合力，這種疫苗極有可能能夠同時對抗多種癌症。 此篇研究的目的在於將兩種或以上的醣抗原連接在一起，並將其接上載體蛋白以形成抗癌疫苗候選物。為了使不同的醣抗原能夠平均接在載體蛋白上，我們將Globo H和SSEA-4這兩種抗原接在一段短胜肽鍵上，使這兩種醣抗原的比例相同，最後和載體蛋白CRM-197(DT)接合，提升此多價抗癌疫苗的免疫性。藉由此合成策略，我們期望能設計出一組多價的抗癌疫苗，能夠有效率的治療不同的癌症。

Most cancer cell lines overexpress specific glycan antigens. Particularly, Globo H, SSEA-3, SSEA-4 of Globo series epitopes are found in at least 16 different types of cancer cell lines but not found in normal ones. The probability of finding one of the three Globo series epitopes in the 16 different types of cancer cell lines is up to 70%. Therefore, they are regarded as potential anticancer vaccine candidates. Most vaccine-associated studies were designed to elicit immune response to a single therapeutic target based on the uniqueness of each antigen. In 2013, our group published a Globo H-DT anticancer vaccine, which could simultaneously induce antibodies against Globo H, SSEA-4, and SSEA-3 antigens, but mostly against Globo H and SSEA-3. To have a universal anti-cancer vaccine, we designed a multivalent vaccine and hope it can induce immune response to all three specific glycan antigens with significantly binding. This multivalent anticancer vaccine can be used to simultaneously target different types of cancer. In this study, we combined two glycan antigens and conjugated the combined antigens with carrier protein to form our target product. In order to evenly attach Globo H and SSEA-4 glycan antigens on the carrier protein, we connected Globo H and SSEA-4 with a short peptide to ensure equal proportions of both antigens. Finally, the glycopeptides were conjugated with the carrier protein CRM-197 (DT) to increase the immunity of this cancer vaccine candidate. We anticipate that this vaccine will be used for early stage treatment and even preventive application.