Cancer Immunol Immun：研究人员积极开发新的抗癌疫苗

近日，Moffitt癌症中心的研究人员给小鼠体内注射一种人工合成疫苗后，发现它能有效杀死人类乳头状瘤病毒导致的癌症。

这项研究结果发表在最近一期​​的Cancer Immunology, Immunotherapy杂志上。

人类乳头状瘤病毒（Human papillomavirus，HPV）是一种嗜上皮性病毒，在人和动物中分布广泛，有高度的特异性，长期以来，已知HPV可引起人类良性的肿瘤和疣，如生长在生殖器官附近皮肤和粘膜上的人类寻常疣、尖锐湿疣以及生长在粘膜上的乳头状瘤。每年导致全球超过250,000人死亡。
 
虽然已有两个批准的用来防止HPV感染导致宫颈癌的人乳头状瘤病毒株的预防性疫苗现在已被广泛使用的，但这些疫苗不能用于治疗人乳头状瘤病毒引起的癌症。因此，有必要开发出治疗HPV相关肿瘤的疫苗。

在努力寻找一个有效的HPV癌症疫苗，消除现有的HPV引起的癌症的过程中，南佛罗里达大学医学院的分子医学大学Kelly Barrios-Marrugo博士等人设计出一个多肽疫苗，名为TriVax-HPV。

当研究人员在人乳头瘤病毒16型诱导的肿瘤小鼠模型上测试该疫苗时，他们发现TriVax小片段包含E7蛋白的合成（肽），会清除小鼠体内的肿瘤，而未接种疫苗的老鼠肿瘤生长速度很快。

作者总结：我们相信这些研究可能有助于推出更有效的微创治疗性疫苗来治疗人乳头状瘤病毒引起的恶性肿瘤。

他们的研究得到了国家卫生研究院RO1CA136828和RO1CA157303项目补助。

doi:10.1007/s00262-012-1259-8
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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-E7_49-57, mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies.

Results

TriVax using HPV16-E7_49-57 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.