Faculty, Staff and Student Publications
Publication Date
5-31-2025
Journal
Stem Cells Translational Medicine
DOI
10.1093/stcltm/szaf020
PMID
40448965
PMCID
PMC12126084
PubMedCentral® Posted Date
5-31-2025
Abstract
Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting. Graft-versus-host disease (GVHD) can be prevented by stimulation of mouse or human memory CD8 T cells against their cognate antigens under cytokine deprivation, in the early phase of culture followed by further expansion with IL21, IL15, and IL7. Thus, human anti-viral CD8 central memory veto T cells generated from CMV and EBV-positive donors are currently evaluated in a clinical trial at MD Anderson Cancer Centre (MDACC). Results in 15 patients indicate a low risk of GVHD. Considering that these cells could offer an attractive platform for CAR cell therapy, we evaluated methodologies for their effective transduction with 2 retroviral vectors. Initially, a vector directed against Her2 was tested and optimal transduction was attained at day 5 of culture. The transduced cells were expanded for an additional 7 days and exhibited marked anti-tumor reactivity ex-vivo while retaining their veto activity. Transduction with a vector directed at CD19 was effectively attained at days 4-5 allowing for substantial harvest of transduced cells at day 12 of culture. These Veto-CD19CAR central memory CD8 T cells exhibited marked anti-tumor reactivity in-vitro and in-vivo without GVHD, measured following transplantation into immune-deficient mice. These results strongly suggest that Veto-CAR T cells offer an attractive platform for CAR T cell therapy without gene editing for addressing the risk of GVHD or graft rejection.
Keywords
Humans, CD8-Positive T-Lymphocytes, Animals, Mice, Immunotherapy, Adoptive, Immunologic Memory, Graft vs Host Disease, Memory T Cells, Female, Receptors, Chimeric Antigen, adult hematopoietic stem cells, cellular therapy, chimeric, clinical translation, immunotherapy, transduction, transplantation, transplantation tolerance
Published Open-Access
yes
Recommended Citation
Liu, Wei-Hsin; Globerson Levin, Anat; Lask, Assaf; et al., "Anti-Viral CD8 Central Memory Veto Cells as a New Platform for Car T Cell Therapy" (2025). Faculty, Staff and Student Publications. 4325.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4325
Graphical Abstract
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