A cancer therapeutic vaccine based on clustered Tn-antigen mimetics induces strong antibody-mediated protective immunity.
A cancer therapeutic vaccine based on clustered Tn-antigen mimetics induces strong antibody-mediated protective immunity.
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DOI：
10.1002/anie.201406897
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发表时间：
2014-10-27
期刊：
影响因子：
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通讯作者：
BenMohamed L
中科院分区：
文献类型：
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作者：
Richichi B;Thomas B;Fiore M;Bosco R;Qureshi H;Nativi C;Renaudet O;BenMohamed L
肿瘤相关碳水化合物抗原(TACA)是肿瘤疫苗的关键成分。各种基于TACA的国产疫苗在临床前动物研究中显示出免疫原性和保护性，但免疫原性较弱、体内不稳定和生物利用度较差，阻碍了它们在临床研究中的进一步评估。我们报道了一种新的“改进的”疫苗原型8，它由四个簇状TN抗原模拟物和一个T辅助细胞肽表位组成，这些表位连接到环肽载体上。疫苗8(I)免疫小鼠是安全的，(Ii)诱导了强大而持久的TN特异性IgM/IgG抗体，能够识别“本地”碳水化合物抗原；(Iii)产生了高滴度的IgG1、IgG2a和IgG3抗体；(Iv)提高了显著的抗体依赖肿瘤消退和保护作用。总而言之，这些发现为疫苗8的临床开发铺平了道路，该疫苗是一种安全有效的针对TN表达的癌症的治疗性疫苗。
Tumor-associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of “native” TACA-based vaccines have shown immunogenicity and protection in pre-clinical animal studies, however the weak immunogenicity, in vivo instability and poor bioavailability, have discouraged their further evaluations in clinical studies. We report on a new “improved” vaccine prototype 8 composed by four clustered Tn-antigen mimetics and a T-helper cell peptide epitope that are conjugated to a cyclopeptide carrier. Immunization of mice with vaccine 8 (i) was safe, (ii) induced a strong and long-lasting Tn-specific IgM/IgG antibodies able to recognize “native” carbohydrate antigens; (iii) produced high titres of IgG1, IgG2a and IgG3 antibodies; (iv) raised a significant antibody-dependent regression of tumors and protection. All together, these findings pave the way for a clinical development of vaccine 8 as a safe and effective therapeutic vaccine against Tn-expressing cancers.