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[Retraction]Anti-inflammatory activity of a short peptide designed for anti-cancer: a beneficial off-target effect of tertomotide

[논문철회]항암백신 tertomotide의 항염활성 연구

  • Lee, Hyosung (Department of Food & Pharmaceutical Science & Engineering, Seowon University)
  • 이효성 (서원대학교 제약식품공학부)
  • Received : 2021.12.05
  • Accepted : 2022.01.20
  • Published : 2022.01.28

Abstract

Tertomotide is a peptide vaccine developed for anti-cancer therapy. Since it has been found to ameliorate inflammatory symptoms in animal studies and clinical test, we investigated anti-inflammation activity of the tertomotide and the mechanism of action in monocyte in order to assess if tertomotide may serve as an anti-inflammatory agent by checking inflammatory cytokines and related signaling pathway following tertomotide treatment. We found that tertomotide reduced the level of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-8 in LPS- or PMA-stimulated monocyte cell line and suppressed NF-κB signaling including the activation of ERK1/2 and P38 MAPK following TNF-α treatment. These results may correlate to the beneficial findings in animal studies, implicating that tertomotide may act as a potential anti-inflammatory agent. This study is an exemplary case for convergence that a computationally designed peptide for immunological purpose exerting unexpected biological activity may elicit novel anti-inflammatory drug.

Tertomotide는 항암제로 개발된 펩타이드 백신이다. 그러나 동물실험과 임상시험에서 염증성 증상이 완화되는 현상이 발견된바 있다. 이에 tertomotide가 항염물질로 작용하는지 확인하기 위하여 직접적인 항염활성과 그 작용기전을 조사하였다. 이를 위해 LPS 또는 PMA에 의해 활성화된 monocyte에 tertomotide를 처리한 후 염증성 cytokine 생산과 관련된 신호전달과정을 관찰하였다. Monocyte에서 tertomotide는 TNF-α, IL-1β, IL-8 등 염증성 싸이토카인의 생산을 감소시켰고 NF-κB 신호를 감쇄시켰으며 또한 TNF-α에 의한 ERK1/2와 P38 MAPK의 활성화를 저해하였다. 이 결과는 tertomotide 처치에 따른 염증성 질환 완화가 NF-κB/STAT3의 신호의 감쇄와 항염활성에 의한 것이라고 설명할 수 있고 이를 활용하여 신규 항염 약물의 도출이 가능할 것으로 판단된다. 이는 면역학적 활성을 목표로 계산화학적으로 설계된 물질의 생물학적 성질을 활용하여 새로운 약물을 도출하는 융합연구의 예시가 될 것이다.

Keywords

References

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