Yong Tracer, Chang Ko-Keng, Wang Yi-Sheng, Ma Che
Genomic Research Center, Academia Sinica, Taipei 11529, Taiwan.
Chemistry Department, National Taiwan University, Taipei 10617, Taiwan.
Vaccines (Basel). 2022 Jan 21;10(2):163. doi: 10.3390/vaccines10020163.
Immune checkpoint inhibitors such as monoclonal antibodies (mAbs) are amongst the most important breakthroughs in cancer therapeutics. However, high cost and short acting time limits its affordability and clinical application. Therefore, an economical and durable alternative is urgently needed. Previously, we identified an IL-17RB targeting mAb which intercepts IL-17B/IL-17RB signal transduction and suppresses tumorigenesis in many types of cancer. We reason that active immunity against the antigenic epitope of IL-17RB can reproduce the anti-cancer effect of mAbs with better sustainability. Here, we present a cancer vaccine composed of multiple synthesized epitope peptides chemically conjugated onto CRM197, a highly immunogenic carrier protein. Combining mass spectrometry with immunoassay, we standardized hapten density determination and optimized vaccine design. Furthermore, orthotopically transplanted syngeneic mouse tumor 4T1 showed that administration of this vaccine therapeutically mitigates primary cancer growth as well as distance metastasis. In conclusion, we demonstrate preparation, characterization and pre-clinical application of a novel peptide cancer vaccine.
免疫检查点抑制剂,如单克隆抗体(mAb),是癌症治疗领域最重要的突破之一。然而,高成本和短效性限制了其可及性和临床应用。因此,迫切需要一种经济且持久的替代方案。此前,我们鉴定出一种靶向IL-17RB的单克隆抗体,它可阻断IL-17B/IL-17RB信号转导,并抑制多种癌症的肿瘤发生。我们推断,针对IL-17RB抗原表位的主动免疫能够重现单克隆抗体的抗癌效果,且可持续性更好。在此,我们展示了一种癌症疫苗,它由化学偶联到CRM197(一种高免疫原性载体蛋白)上的多个合成表位肽组成。结合质谱分析和免疫测定,我们规范了半抗原密度测定并优化了疫苗设计。此外,原位移植同基因小鼠肿瘤4T1实验表明,接种这种疫苗可在治疗上减轻原发性癌症的生长以及远处转移。总之,我们展示了一种新型肽癌症疫苗的制备、表征和临床前应用。