Seminar

Seminar

Chimeric T Cells and Macrophages: Cell Engineering to Expand Their Therapeutic Potentials

  • POSTED DATE : 2023-05-12
  • WRITER : 화학과
  • HIT : 1911
  • DATE : 2023년 5월 18일(목)오후 4시 30분
  • PLACE : 330226호실

화학과 세미나가 다음주 목요일(5월 18일) 오후 4시 30분에 개최됩니다.

많은 참여 부탁드립니다.


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제  목 : Chimeric T Cells and Macrophages: Cell Engineering to Expand Their Therapeutic Potentials


연  사 : 박희호 교수님(한양대학교 생명공학과)


일  시 : 2023년 5월 18일(목)오후 4시 30분


장  소 : 화학관 2층 330226호실

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Chimeric T Cells and Macrophages:

Cell Engineering to Expand Their Therapeutic Potentials

 

Hee Ho Park 1,*

1 Department of Bioengineering, Hanyang University,

Seoul 04763, Republic of Korea

parkhh@hanyang.ac.kr

 

 

Chimeric antigen receptor-T (CAR-T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to its complex ex vivo cell-manufacturing procedures and low therapeutic efficacy against solid tumors. The limited therapeutic effects are partially due to limited CAR-T cell infiltration to solid tumors and inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented to in vivo program macrophages, which can intrinsically penetrate solid tumors, into CAR-M1 macrophages displaying enhanced cancer-directed phagocytosis and antitumor activity. In vivo injected nanocomplexes of macrophage-targeting nanocarriers and CAR-interferon-γ-encoding plasmid DNA induce CAR-M1 macrophages that are capable of CAR-mediated cancer phagocytosis, antitumor immunomodulation, and inhibition of solid tumor growth. Together, this study describes an off-the-shelf CAR-macrophage therapy that is effective for solid tumors and avoids the complex and costly processes of ex vivo CAR-cell manufacturing.

  Severe infectious diseases, such as coronavirus disease 2019 (COVID-19), can induce hypercytokinemia and multiple organ failure. In spite of the growing demand for peptide therapeutics against infectious diseases, current small molecule-based strategies still require frequent administration due to limited half-life and enzymatic digestion in blood. To overcome this challenge, a strategy to continuously express multi-level therapeutic peptide drugs on the surface of immune cells, is established. Here, chimeric T cells stably expressing therapeutic peptides are presented for treatment of severe infectious diseases. Using lentiviral system, T cells are engineered to express multi-level therapeutic peptides with matrix metallopeptidases- (MMP-) and tumor necrosis factor alpha converting enzyme- (TACE-) responsive cleavage sites on the surface. The enzymatic cleavage releases �-carboxyglutamic acid of protein C (PC-Gla) domain and thrombin receptor agonist peptide (TRAP), which activate endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), respectively. These chimeric T cells prevent vascular damage in tissue -engineered blood vessel and suppress hypercytokinemia and lung tissue damages in vivo, demonstrating promise for use of engineered T cells against sepsis and other infectious-related diseases.



* 졸업논문 교과목 수강자 세미나 필수 참석 안내
석사, 석박통합, 박사과정이 수강하는 <졸업논문연구학점 1~6>수강자는 학과에서 개최하는 목요일 정규세미나에 반드시 참석해야함.

관련공지(skku.edu)https://skb.skku.edu/chem/News/notice.do?mode=view&articleNo=146936&article.offset=10&articleLimit=10)