Earticle

초록

영어

Several advances in anticancer therapy have demonstrated significant improvements in clinical outcomes, and adoptive cell therapy has emerged as a type of immunotherapy that can modulate immune responses by transferring engineered immune cells. However, it remains a challenge because only a small percentage of respondents have responded. Three-dimensional (3D) in vitro models of the tumor microenvironment (TME) have the potential to provide a platform for assessing and predicting responses to therapy. Here, we propose an in vitro 3D tumor model with clusters of colorectal cancer (CRC) cells around perfusable vascular networks to evaluate immune cell-mediated cytotoxicity against cancer cells. A 3D injection-molded co-culture model consists of 28 microwells where identical vascularized cancer models can be formed in separate wells. It allows robust hydrogel patterning, resulting in high-throughput experiments. Compared to the polydimethylsiloxane (PDMS)-based microfluidic devices, our devices allowed a greater number of experiments to be conducted. A permeability test was also conducted to confirm the characteristics of the tumor vasculature. Primary natural killer (NK) cells were introduced into a tumor vascularized network and monitored using live-cell imaging. The extravasation, migration, and cytotoxic activity of six types of CRC cell lines were examined. Based on the consensus molecular subtypes (CMS) of CRC with distinct immune responses, CMS1 cancer cells were most susceptible to NK cell cytotoxicity. This study indicates the potential of our vascularized tumor model in assessing the responses to adoptive cell therapy by understanding the various steps involved in the immune response.

저자

• Jiyoung Song [ Brain Science Institute Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea ]
• Hyeri Choi [ Department of Mechanical Engineering, Seoul National University, Seoul, Republic of Korea ]
• Seung Kwon Koh [ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea ]
• Dohyun Park [ Department of Mechanical Engineering, Seoul National University, Seoul, Republic of Korea ]
• Youngtaek Kim [ Department of Mechanical Engineering, Seoul National University, Seoul, Republic of Korea ]
• Duck Cho [ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea, Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ]
• Noo Li Jeon [ Department of Mechanical Engineering, Seoul National University, Institute of Advanced Machines and Design (SNU-IAMD), Seoul National University, Seoul, South Korea ] Corresponding Author

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614