Department of Immunology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
National Clinical Research Center for Cancer, Tianjin, China.
Front Immunol. 2018 Mar 7;9:335. doi: 10.3389/fimmu.2018.00335. eCollection 2018.
Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 ( < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group ( < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines.
由于关于黑猩猩腺病毒血清型 68（AdC68）的基于疫苗的临床前结果显示出令人鼓舞的结果，这提醒我们 AdC68 可能是一种合适的癌症疫苗载体。先前的研究表明，癌症患者和健康志愿者之间针对腺病毒的中和抗体（NAb）的血清流行率不同。关于癌症患者对 AdC68 的 NAb 流行率的知识还很缺乏。因此，评估癌症患者中针对 AdC68 的 NAb 的预先存在情况，可以为开发未来的基于 AdC68 的癌症疫苗提供有用的见解。在这项研究中，招募了 440 名患有不同病理类型肿瘤的患者和 204 名健康成年志愿者，以评估针对 AdC68 和人腺病毒血清型 5（AdHu5）的 NAb。针对 AdC68 的 NAb 的血清流行率明显低于癌症患者中针对 AdHu5 的 NAb（43.64%对 67.05%，<0.01）。癌症患者中针对 AdC68 的 NAb 的血清流行率明显高于健康成年志愿者中检测到的 NAb（43.64%对 23.53%，=0.000）。与口咽癌、结肠癌和直肠癌患者相比，肺癌、喉癌、食管癌和宫颈癌患者的 AdC68 NAb 血清流行率要低得多。此外，肺腺癌患者中针对 AdC68 的 NAb 血清流行率明显低于肺鳞癌患者（35.00%对 70.00%，<0.05）。未发现癌症患者不同临床分期之间的 AdC68 NAb 存在差异。在癌症 I 期、II 期和 III 期患者中，针对 AdC68 的 NAb 百分比明显低于针对 AdHu5 的 NAb 百分比（<0.05）。在癌症 IV 期患者中，针对 AdC68 和 AdHu5 的 NAb 百分比之间未发现差异。该研究还证明了针对阳性样本的 AdHu5 和 AdC68 NAb 滴度的分布。结果表明，与健康受试者和癌症受试者中的 AdHu5 相比，针对 AdC68 的 NAb 滴度非常低，尤其是在肺癌、喉癌、食管癌、胃癌和宫颈癌患者中。此外，针对 AdC68 的 NAb 滴度在同一临床分期和年龄组中明显低于针对 AdHu5 的 NAb 滴度（<0.05）。综上所述，本研究表明，针对 AdC68 的 NAb 明显低于针对 AdHu5 的 NAb，尤其是在肺腺癌、喉癌、食管癌和宫颈癌患者中。这些结果为 AdC68 作为合适的癌症疫苗载体提供了有力支持。
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