1 option
The BTLA-HVEM Axis Restrains Chimeric Antigen Receptor T Cells Against Cancer / Puneeth Guruprasad.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Guruprasad, Puneeth, author.
- Language:
- English
- Subjects (All):
- Bioengineering.
- Cellular biology.
- Oncology.
- Immunology.
- Bioengineering--Penn dissertations.
- Penn dissertations--Bioengineering.
- Local Subjects:
- Bioengineering.
- Cellular biology.
- Oncology.
- Immunology.
- Bioengineering--Penn dissertations.
- Penn dissertations--Bioengineering.
- Physical Description:
- 1 online resource (201 pages)
- Contained In:
- Dissertations Abstracts International 85-12B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- Language Note:
- English
- Summary:
- The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment (TME). We leveraged single-cell RNA sequencing to deconvolute the TME of Hodgkin lymphoma, an ideal model given the extensive degree of immunosuppressive cell infiltration. Using an algorithm to infer cell-to-cell communication, we identified a predominant role of the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive cells, such regulatory T cells and tumor-associated monocytes. Correspondingly, we found that high BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor response to treatment. Therefore, we performed CRISPR-Cas9 knockout of BTLA in CAR T cells and demonstrated improved tumor control and persistence in models of Hodgkin lymphoma, non-Hodgkin lymphoma, and solid malignancies. Overall, our data suggest that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of novel strategies to overcome this barrier.
- Notes:
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- Advisors: Ruella, Marco; Committee members: Hammer, Daniel; Shaffer, Sydney; Fraietta, Joseph; Schuster, Stephen J.
- Department: Bioengineering.
- Ph.D. University of Pennsylvania 2024.
- Local Notes:
- School code: 0175
- ISBN:
- 9798382830513
- Access Restriction:
- Restricted for use by site license.
- This item is not available from ProQuest Dissertations & Theses.
The Penn Libraries is committed to describing library materials using current, accurate, and responsible language. If you discover outdated or inaccurate language, please fill out this feedback form to report it and suggest alternative language.