Personalized Peptide Vaccine for Treatment of Advanced Cancer
Personalized Peptide Vaccine for Treatment of Advanced Cancer
复制标题
DOI：
10.2174/0929867321666140205132936
复制
发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Itoh, Kyogo
中科院分区：
文献类型：
--
作者：
Sasada, Tetsuro;Yamada, Akira;Itoh, Kyogo
在过去的20年里，癌症免疫治疗领域取得了巨大的进步，因为许多肿瘤相关抗原（TAA）已被确定。尽管已经开发和临床检查了用于治疗性癌症免疫疗法的各种方法，包括基于肽的疫苗，但是肿瘤细胞特征和宿主免疫细胞库的复杂性和多样性似乎限制了这种治疗方式的治疗功效。考虑到针对异质性肿瘤细胞的免疫应答的多样性，为个体患者定制合适的疫苗抗原的选择可能是开发有效的癌症疫苗的合理方法。我们已经开发了一种称为个性化肽疫苗（PPV）的新的免疫方法，其中最多四个人类白细胞抗原（HLA）匹配的疫苗肽是根据预先存在的宿主免疫接种前选择的。我们进行了一系列PPV的I期和II期临床试验，这些试验在各种晚期癌症患者中显示出更好的抗原特异性免疫应答和有希望的临床结局。建议进行进一步的随机III期试验，以证明PPV的临床获益。此外，用于选择PPV获益最大的患者的新型生物标志物仍有待确定。
The field of cancer immunotherapy has moved forward drastically in the past 20 years, since many tumorassociated antigens (TAA) have been identified. Although various approaches for therapeutic cancer immunotherapies, including peptide-based vaccines, have been developed and clinically examined, the complexity and diversity of tumor cell characteristics and host immune cell repertoires seem to limit the therapeutic efficacy of this treatment modality. Considering the diversity of immune responses against heterogeneous tumor cells, tailored selections of vaccine antigens appropriate for individual patients could be a rational approach for developing effective cancer vaccines. We have developed a novel immunotherapeutic approach called personalized peptide vaccine (PPV), in which a maximum of four human leukocyte antigen (HLA)-matched vaccine peptides were selected based on the pre-existing host immunity before vaccination. We conducted a series of phase I and phase II clinical trials of PPV, which have shown better antigen-specific immune responses and promising clinical outcomes in patients with various types of advanced cancers. Further randomized phase III trials would be recommended to prove the clinical benefits of PPV. In addition, novel biomarkers for selecting patients who would benefit most from PPV remain to be identified.