인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Mesothelin (MSLN) is a prominent target antigen for CAR T cell therapy due to its extensive expression in various solid tumors, including pancreatic cancer. However, the therapeutic efficacy of MSLN-targeted CAR T cell therapy has been limited in clinical trials for pancreatic cancer, often resulting in temporary stable disease as the best response. The heterogeneous expression of MSLN and its loss over time, along with the immunosuppressive tumor microenvironment (TME), are key factors restricting effectiveness. Oncolytic viruses are emerging cancer therapies that replicate in tumor cells and remodel the TME into an immunogenic state. Here, we engineered an oncolytic herpes simplex virus type 1 expressing human MSLN (HSV-MSLN) and evaluated its combination with MSLN-CAR T cells in a murine pancreatic ductal adenocarcinoma model. In vitro, HSV-MSLN effectively induced MSLN expression on murine pancreatic cancer cells, with subsequent cell lysis. In co-culture, HSV-MSLN-infected cancer cells activated MSLN-CAR T cells, which effectively eliminated the infected cells. In vivo, HSV-MSLN delivered MSLN on the tumor cell surface and reprogrammed the TME toward an immunogenic state. The combination therapy significantly enhanced antitumor efficacy, inducing activated, proliferative CD8<sup>+</sup> CAR T cells and reducing PD-1<sup>+</sup>TIM-3<sup>+</sup> exhausted endogenous CD8<sup>+</sup> T cells and regulatory T cells in tumors. Furthermore, the combination therapy increased migratory XCR1<sup>+</sup>CD103<sup>+</sup> dendritic cells (DCs) in tumors and tumor-draining lymph nodes (TDLNs) while expanding CD44<sup>+</sup>CD8<sup>+</sup> T cells with central and effector memory phenotypes. Taken together, these results demonstrate that HSV-MSLN reprograms immune cells in the TME and TDLNs and synergizes with MSLN-CAR T cells to enhance antitumor responses, leading to a more robust therapeutic effect.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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