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Improving CAR T Cell Persistence in Pancreatic Cancer Using an In Vivo CRISPR Knockout Screen
Improving CAR T Cell Persistence in Pancreatic Cancer Using an In Vivo CRISPR Knockout Screen
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202102957
- ISBN
- 9798280712140
- DDC
- 616.079
- 저자명
- Kienka, Tamina.
- 서명/저자
- Improving CAR T Cell Persistence in Pancreatic Cancer Using an In Vivo CRISPR Knockout Screen
- 발행사항
- [Sl] : Harvard University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 121 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Maus, Marcela V.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2024.
- 초록/해제
- 요약Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success in treating a subset of hematologic malignancies. However, efficacy against solid tumors has remained limited owing, in part, to the poor CAR T cell persistence in the immunosuppressive solid tumor microenvironment. Preclinical CRISPR screening studies have improved our understanding of the mechanisms that regulate CAR T cell exhaustion. However, such work has primarily been conducted in vitro, failing to reproduce the complex challenge of the hypoxic, cytokine-depleted vivo tumor microenvironment. Here, we perform in vivo CAR T cell CRISPR knockout screens (14 or 28-day CAR engraftment) in pancreatic adenocarcinoma using a curated Mario guide library to identify genes that enhance CAR T cell persistence in vivo. Results suggest a temporal progression to the enrichment of gene hits. The short-term, 14-day Mario screen may have identified hits that improve the short-term enrichment of Mesothelin CAR T cells. However, the 28-day screen identified gene knockouts implicated in the JAK-STAT signaling pathway, such as SOCS1 and PTPN2, which demonstrate more durable tumor control.
- 일반주제명
- Immunology
- 일반주제명
- Cellular biology
- 일반주제명
- Oncology
- 키워드
- T cell therapy
- 기타저자
- Harvard University Medical Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aKienka, Tamina.▼0(orcid)0000-0003-1551-0057
■24510▼aImproving CAR T Cell Persistence in Pancreatic Cancer Using an In Vivo CRISPR Knockout Screen
■260 ▼a[Sl]▼bHarvard University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a121 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Maus, Marcela V.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2024.
■520 ▼aChimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success in treating a subset of hematologic malignancies. However, efficacy against solid tumors has remained limited owing, in part, to the poor CAR T cell persistence in the immunosuppressive solid tumor microenvironment. Preclinical CRISPR screening studies have improved our understanding of the mechanisms that regulate CAR T cell exhaustion. However, such work has primarily been conducted in vitro, failing to reproduce the complex challenge of the hypoxic, cytokine-depleted vivo tumor microenvironment. Here, we perform in vivo CAR T cell CRISPR knockout screens (14 or 28-day CAR engraftment) in pancreatic adenocarcinoma using a curated Mario guide library to identify genes that enhance CAR T cell persistence in vivo. Results suggest a temporal progression to the enrichment of gene hits. The short-term, 14-day Mario screen may have identified hits that improve the short-term enrichment of Mesothelin CAR T cells. However, the 28-day screen identified gene knockouts implicated in the JAK-STAT signaling pathway, such as SOCS1 and PTPN2, which demonstrate more durable tumor control.
■590 ▼aSchool code: 0084.
■650 4▼aImmunology
■650 4▼aCellular biology
■650 4▼aOncology
■653 ▼aT cell therapy
■653 ▼aTumor microenvironment
■653 ▼aHematologic malignancies
■653 ▼aTemporal progression
■690 ▼a0982
■690 ▼a0379
■690 ▼a0992
■71020▼aHarvard University▼bMedical Sciences.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356582▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
