"評估在犬隻腫瘤上使用VEGF, EGF, EGFR異種模擬表位DNA疫苗的效果"

Abstract

在幾個犬隻腫瘤中，已經發現幾種過度表現的物質與腫瘤惡性程度相關：表皮生長因子（EGF），表皮生長因子受體（EGFR）和血管內皮生長因子（VEGF）。本研究目的是評估對腫瘤患犬施打異種三合一 DNA疫苗使病患產生體液免疫反應對抗中和血中生長因子抑制腫瘤表面受器。此三合一疫苗是由VEGF, EGF, EGFR模擬表位的結構所組成。共計有十四隻狗參加治療計畫，有6隻為鼻腔腫瘤、3隻是尾肛周邊腫瘤，還有5隻是其他種類的上皮癌。所有患犬間隔兩周施打一次疫苗，同時在每次注射前收集血液樣本，總共十次注射。接種疫苗後針對血清中的抗體波動，使用ELISA進行檢測。其中判定對於疫苗有免疫反應的犬隻為9隻，反應率為64%，而中位生存時間為538天，明顯比沒有反應組來的高(192天)。免疫反應陽性的患者雖然沒有明顯腫瘤消退的情況，不過都處在病情穩定的情況下，雖然疫苗所引發的抗體只有輕微升高。其中產生抗EGFR抗體的病患有十五倍的機會能達到病情穩定。此外，我們意外發現了，平均紅血球血紅素(MCH)和嗜中性球與淋巴球的比例(NLR)可能可以做為免疫治療成效的監測指標。處於病情穩定的患者其起始MCH都較高；另外如果免疫反應陽性的病患其NLR明顯下降表示免疫系統被疫苗活化。總體而言，異種三合一DNA疫苗是能夠激活免疫系統，同時延長病患的生存時間，但需要改良疫苗注射計畫以激發出更強的免疫反應。

The over expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are observed in several canine tumors which are associated with malignancy. The aim of this research is to evaluate the humoral immune response induced by a xenogeneic 3-in-1 DNA vaccine on tumor-bearing dogs. This DNA vaccine consists of the constructs of human EGF, VEGF and EGFR mimotope as antigen. Fourteen dogs with tumor were enrolled in this study. Each patient received a total of ten times vaccine injections with 2 weeks interval and blood sample was collected at the time of each injection. Monitoring of post vaccination serum antibody production potency is performed by ELISA test during the entire procedure. Fourteen dogs finished vaccine protocol and median survival time of positive immune response group was 538 days. Patient with positive immune response achieved stable disease with mild elevated antibody titer. Interestingly, MCH and variation of neutrophil lymphocyte ratio were two promising indicators of immune therapy. Patients with higher MCH and decline NLR after vaccination exhibit longer survival time. Overall, xenogeneic 3-in-1 DNA vaccine did activate immune system but reinforcement of vaccine protocol was needed.