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Activation-Dependent Lentiviruses Promote Selective Expansion and Transduction of Antigen-Specific T Cells
Activation-Dependent Lentiviruses Promote Selective Expansion and Transduction of Antigen-Specific T Cells
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103556
- ISBN
- 9798280713246
- DDC
- 616.079
- 서명/저자
- Activation-Dependent Lentiviruses Promote Selective Expansion and Transduction of Antigen-Specific T Cells
- 발행사항
- [Sl] : Harvard University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 141 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: A.
- 주기사항
- Advisor: Dougan, Stephanie;Birnbaum, Michael.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2025.
- 초록/해제
- 요약Tumor-infiltrating lymphocyte (TIL) therapy has shown recent promise in the treatment of advanced melanoma. However, current manufacturing pipelines make use of bulk-expanded TILs, without the ability to select for bona fide tumor-reactive clonotypes. Thus, new methodologies are required to enhance the selectivity and potency of autologous TILs, while leaving bystander T cells untouched. Here, we demonstrate an approach to target recently-activated T cells via display of agonistic ligands that bind to a marker of early T cell activation (4-1BB, CD137) on the surface of a lentiviral (LV) particle. These pseudotyped LV vectors specifically recognize human 4-1BB in cell lines and primary T cells, promoting the selective activation and expansion of antigen-specific T cells from rare starting populations after antigen stimulation. Moreover, anti-4-1BB LVs specifically transduce antigen-specific T cells with user-defined genetic cargoes that can be used to both track individual clonotypes via single-cell sequencing and enhance their cytotoxic function to extend survival in a xenograft model of human melanoma. We also demonstrate that anti-4-1BB LVs can be directly added to tumor-associated lymphocytes and TIL-containing tumor fragments, promoting the transduction of patient-specific T cells ex vivo. Overall, this platform offers the ability to target antigen-specific T cells (CD4+, CD8+) in an antigen-agnostic, MHC-independent manner with potential applications in adoptive cell therapy manufacturing pipelines and TCR identification efforts.
- 일반주제명
- Immunology
- 일반주제명
- Cellular biology
- 일반주제명
- Therapy
- 일반주제명
- Molecular biology
- 키워드
- Immunotherapy
- 기타저자
- Harvard University Immunology
- 기본자료저록
- Dissertations Abstracts International. 86-12A.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798280713246
■035 ▼a(MiAaPQ)AAI32042081
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aSmith, Blake Edward.▼0(orcid)0000-0001-9878-8198
■24510▼aActivation-Dependent Lentiviruses Promote Selective Expansion and Transduction of Antigen-Specific T Cells
■260 ▼a[Sl]▼bHarvard University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a141 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: A.
■500 ▼aAdvisor: Dougan, Stephanie;Birnbaum, Michael.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2025.
■520 ▼aTumor-infiltrating lymphocyte (TIL) therapy has shown recent promise in the treatment of advanced melanoma. However, current manufacturing pipelines make use of bulk-expanded TILs, without the ability to select for bona fide tumor-reactive clonotypes. Thus, new methodologies are required to enhance the selectivity and potency of autologous TILs, while leaving bystander T cells untouched. Here, we demonstrate an approach to target recently-activated T cells via display of agonistic ligands that bind to a marker of early T cell activation (4-1BB, CD137) on the surface of a lentiviral (LV) particle. These pseudotyped LV vectors specifically recognize human 4-1BB in cell lines and primary T cells, promoting the selective activation and expansion of antigen-specific T cells from rare starting populations after antigen stimulation. Moreover, anti-4-1BB LVs specifically transduce antigen-specific T cells with user-defined genetic cargoes that can be used to both track individual clonotypes via single-cell sequencing and enhance their cytotoxic function to extend survival in a xenograft model of human melanoma. We also demonstrate that anti-4-1BB LVs can be directly added to tumor-associated lymphocytes and TIL-containing tumor fragments, promoting the transduction of patient-specific T cells ex vivo. Overall, this platform offers the ability to target antigen-specific T cells (CD4+, CD8+) in an antigen-agnostic, MHC-independent manner with potential applications in adoptive cell therapy manufacturing pipelines and TCR identification efforts.
■590 ▼aSchool code: 0084.
■650 4▼aImmunology
■650 4▼aCellular biology
■650 4▼aTherapy
■650 4▼aMolecular biology
■653 ▼aAdoptive cell therapy
■653 ▼aAntigen-specific T cells
■653 ▼aImmunoengineering
■653 ▼aImmunotherapy
■653 ▼aLentiviral surface display
■653 ▼aTumor-infiltrating lymphocyte
■690 ▼a0982
■690 ▼a0379
■690 ▼a0212
■690 ▼a0307
■71020▼aHarvard University▼bImmunology.
■7730 ▼tDissertations Abstracts International▼g86-12A.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357759▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
