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Safe engineering of...
Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer
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- Jin, Chuan (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Magnus Essand group
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- Fotaki, Grammatiki (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Magnus Essand group
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- Ramachandran, Mohanraj (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Magnus Essand group
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- Nilsson, Berith (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Magnus Essand group
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- Essand, Magnus (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Magnus Essand group
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- Yu, Di (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Magnus Essand group
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(creator_code:org_t)
- 2016-05-06
- 2016
- Engelska.
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 8:7, s. 702-711
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Chimeric antigen receptor (CAR) T-cell therapy is a new successful treatment for refractory B-cell leukemia. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. Herein, we describe a novel episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element, for either expression of transgenes or silencing of target genes. The insertional events of this vector into the genome of host cells are below detection level. CD19 CAR T cells engineered with a NILV-S/MAR vector have similar levels of CAR expression as T cells engineered with an integrating LV vector, even after numerous rounds of cell division. NILV-S/MAR-engineered CD19 CAR T cells exhibited similar cytotoxic capacity upon CD19(+) target cell recognition as LV-engineered T cells and are as effective in controlling tumor growth in vivo We propose that NILV-S/MAR vectors are superior to current options as they enable long-term transgene expression without the risk of insertional mutagenesis and genotoxicity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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