4.7 Article

Active Humoral Response Reverts Tumorigenicity through Disruption of Key Signaling Pathway

期刊

VACCINES
卷 10, 期 2, 页码 -

出版社

MDPI
DOI: 10.3390/vaccines10020163

关键词

immunotherapy; peptide cancer vaccine; B-cell cancer vaccine; CRM197; IL-17RB; MALDI-TOF-MS; hapten density

资金

  1. Academia Sinica Genomics Research Center

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This article introduces the preparation and clinical application of a cancer vaccine targeting IL-17RB. The vaccine is composed of multiple synthesized epitope peptides chemically conjugated onto CRM197, a carrier protein, and has a durable anti-cancer effect.
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.

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