近日，Moffitt癌癥中心的研究人員給小鼠體內(nèi)注射一種人工合成疫苗后,，發(fā)現(xiàn)它能有效殺死人類乳頭狀瘤病毒導致的癌癥,。
這項研究結(jié)果發(fā)表在最近一期的Cancer Immunology, Immunotherapy雜志上。
人類乳頭狀瘤病毒（Human papillomavirus,，HPV）是一種嗜上皮性病毒,，在人和動物中分布廣泛，有高度的特異性,，長期以來,，已知HPV可引起人類良性的腫瘤和疣，如生長在生殖器官附近皮膚和粘膜上的人類尋常疣,、尖銳濕疣以及生長在粘膜上的乳頭狀瘤,。每年導致全球超過250,000人死亡。
雖然已有兩個批準的用來防止HPV感染導致宮頸癌的人乳頭狀瘤病毒株的預防性疫苗現(xiàn)在已被廣泛使用的,，但這些疫苗不能用于治療人乳頭狀瘤病毒引起的癌癥,。因此，有必要開發(fā)出治療HPV相關(guān)腫瘤的疫苗,。
在努力尋找一個有效的HPV癌癥疫苗,，消除現(xiàn)有的HPV引起的癌癥的過程中，南佛羅里達大學醫(yī)學院的分子醫(yī)學大學Kelly Barrios-Marrugo博士等人設(shè)計出一個多肽疫苗,，名為TriVax-HPV,。
當研究人員在人乳頭瘤病毒16型誘導的腫瘤小鼠模型上測試該疫苗時,，他們發(fā)現(xiàn)TriVax小片段包含E7蛋白的合成（肽），會清除小鼠體內(nèi)的腫瘤,，而未接種疫苗的老鼠腫瘤生長速度很快,。
作者總結(jié)：我們相信這些研究可能有助于推出更有效的微創(chuàng)治療性疫苗來治療人乳頭狀瘤病毒引起的惡性腫瘤。
他們的研究得到了國家衛(wèi)生研究院RO1CA136828和RO1CA157303項目補助,。（生物谷：Bioon.com）
doi:10.1007/s00262-012-1259-8
PMC:
PMID:
TriVax-HPV: an improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers
Kelly Barrios, Esteban Celis
Therapeutic vaccines for cancer are an attractive alternative to conventional therapies, since the later result in serious adverse effects and in most cases are not effective against advanced disease. Human papillomavirus (HPV) is responsible for several malignancies such as cervical carcinoma. Vaccines targeting oncogenic viral proteins like HPV16-E6 and HPV16-E7 are ideal candidates to elicit strong immune responses without generating autoimmunity because: (1) these products are not expressed in normal cells and (2) their expression is required to maintain the malignant phenotype. Our group has developed peptide vaccination strategy called TriVax, which is effective in generating vast numbers of antigen-specific T cells in mice capable of persisting for long time periods.
Materials and methods
We have used two HPV-induced mouse cancer models (TC-1 and C3.43) to evaluate the immunogenicity and therapeutic efficacy of TriVax prepared with the immunodominant CD8 T-cell epitope HPV16-E749-57, mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies.
Results
TriVax using HPV16-E749-57 induced large and persistent T-cell responses that were therapeutically effective against established HPV16-E7 expressing tumors. In most cases, TriVax was successful in attaining complete rejections of 6–11-day established tumors. In addition, TriVax induced long-term immunological memory, which prevented tumor recurrences. The anti-tumor effects of TriVax were independent of NK and CD4 T cells and, surprisingly, did not rely to a great extent on type-I or type-II interferon.
Conclusions
These findings indicate that the TriVax strategy is an appealing immunotherapeutic approach for the treatment of established viral-induced tumors. We believe that these studies may help to launch more effective and less invasive therapeutic vaccines for HPV-mediated malignancies.
