Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent

Lévy, Camille; Amirache, Fouzia; Girard-Gagnepain, Anais; Frecha, Cecilia; Roman-Rodriguez, Francisco J; Bernadin, Ornéllie; Costa, Caroline; Nègre, Didier; Gutiérrez‐Guerrero, Alejandra; Vranckx, Lenard; Clerc, Isabelle; Taylor, Naomi; Thielecke, Lars; Cornils, Kerstin; Bueren, Juan A.; Rı́o, Paula; Gijsbers, Rik; Cosset, François‐Loïc; Verhoeyen, Els

doi:10.1182/bloodadvances.2017007773

Cited by 39 publications

(32 citation statements)

References 76 publications

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“…An UCOE sequence(10) was added to the lentiviral vector pHRSIN-SFFV-eGFP(11) upstream of the SFFV promoter to produce pHUS-GFP vector. For the CAR-expression vector, GFP in pHUS-GFP was replaced by an anti-CD22 CAR (m971 ScFv) fused to 28z and BBz (Dr. Orentas, National Cancer Institute).…”

Section: Methodsmentioning

confidence: 99%

Efficient and robust NK-Cell transduction with Baboon Envelope pseudotyped lentivector: a major tool for immunotherapy

Lemieux

Bifsha

et al. 2019

Preprint

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NK-cell resistance to transduction is a major technical hurdle for developing NK-cell immunotherapy. By using Baboon envelope pseudotyped lentiviral vectors (BaEV-LVs) encoding eGFP, we obtained a transduction rate of 23.0±6.6% in freshly-isolated NK-cells (FI-NK) and 83.4±10.1% in NK-cells obtained from the NK-cell Activation and Expansion System (NKAES), even at low MOI, with a sustained transgene expression for at least 21 days. BaEV-LVs outperformed Vesicular Stomatitis Virus type-G (VSV-G)-, RD114-and Measles Virus (MV)-pseudotyped LVs (p<0.001). mRNA expression of both BaEV receptors, ASCT1 and ASCT2, was detected in FI-NK and NKAES, with much higher expression in NKAES. Transduction with BaEV-LVs encoding for CAR-CD22 resulted in robust CAR-expression on 44.2%±14.2% of NKAES cells, which allowed the specific killing of the NK-resistant pre-B-ALL-RS4;11 cell line. Using a larger vector, encoding a dual CD19/CD22-CAR separated by T2A, we were able to transduce and re-expand dual-CAR-expressing NKAES, even with low viral titer. These dual-CAR-NK efficiently and specifically killed both CD19KO-and CD22KO-RS4;11 cells, which may overcome antigen-loss escape in the clinical setting. Our results suggest that BaEV-LVs may efficiently enable NK-cell biological studies and translation of NK-cell-based immunotherapy to the clinic.

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Section: Methodsmentioning

confidence: 99%

Efficient and robust NK-Cell transduction with Baboon Envelope pseudotyped lentivector: a major tool for immunotherapy

Lemieux

Bifsha

et al. 2019

Preprint

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“…In the case of unstimulated HSCs, the transduction levels reached 70%. It was further demonstrated that these high levels were maintained or increased even after successive rounds of engraftment in NOD/SCIDγC −/− (NSG) mice [47]. These results indicated that high levels of HSCs were transduced.…”

Section: Pseudotyping Lvs With H and F Glycoprotein From Measles Virusmentioning

confidence: 90%

“…These two viruses are stable in human and macaque sera, giving them a great potential for in vivo gene therapy. They also recognize the sodium-dependent neutral amino acid transport (ASCT-2) in human cells, but only BaEV also recognizes ASCT-1, giving BaEV a wider tropism [47,52]. ASCT-1 and -2 receptors have a 57% identical sequence, and they are expressed in a wide number of cells.…”

Section: Pseudotyping Of Lvs With Baboon Endogenous Virus and Feline mentioning

confidence: 99%

Lentiviral Vector Pseudotypes: Precious Tools to Improve Gene Modification of Hematopoietic Cells for Research and Gene Therapy

Gutiérrez‐Guerrero

Cosset

Verhoeyen

2020

Viruses

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Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived from the human immune deficiency virus allowing efficient gene transfer in mammalian cells. They represent one of the safest and most efficient treatments for monogenic diseases affecting the hematopoietic system. LVs are modified with different viral envelopes (pseudotyping) to alter and improve their tropism for different primary cell types. The vesicular stomatitis virus glycoprotein (VSV-G) is commonly used for pseudotyping as it enhances gene transfer into multiple hematopoietic cell types. However, VSV-G pseudotyped LVs are not able to confer efficient transduction in quiescent blood cells, such as hematopoietic stem cells (HSC), B and T cells. To solve this problem, VSV-G can be exchanged for other heterologous viral envelopes glycoproteins, such as those from the Measles virus, Baboon endogenous retrovirus, Cocal virus, Nipah virus or Sendai virus. Here, we provide an overview of how these LV pseudotypes improved transduction efficiency of HSC, B, T and natural killer (NK) cells, underlined by multiple in vitro and in vivo studies demonstrating how pseudotyped LVs deliver therapeutic genes or gene editing tools to treat different genetic diseases and efficiently generate CAR T cells for cancer treatment.

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“…Besides LV-mediated gene transfer, other vectors are being investigated, such as foamy viral vectors [225], and measles virus envelope pseudotyped LVs [226]. HDAd5/35++ vectors also represent a promising strategy-particularly of relevance for in vivo HSC transduction.…”

Section: Fanconi Anemiamentioning

confidence: 99%

Adenovirus vectors in hematopoietic stem cell genome editing

Lieber

2019

FEBS Letters

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Genome editing of hematopoietic stem cells (HSCs) represents a therapeutic option for a number of hematological genetic diseases, as HSCs have the potential for self-renewal and differentiation into all blood cell lineages. This review presents advances of genome editing in HSCs utilizing adenovirus vectors as delivery vehicles. We focus on capsid-modified, helper-dependent adenovirus vectors that are devoid of all viral genes and therefore exhibit an improved safety profile. We discuss HSC genome engineering for several inherited disorders and infectious diseases including hemoglobinopathies, Fanconi anemia, hemophilia, and HIV-1 infection by ex vivo and in vivo editing in transgenic mice, nonhuman primates, as well as in human CD34 + cells. Mechanisms of therapeutic gene transfer including episomal expression of designer nucleases and base editors, transposase-mediated random integration, and targeted homology-directed repair triggered integration into selected genomic safe harbor loci are also reviewed.

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Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent

Abstract: Key Points H/F-LVs permit very-high-level transduction of human HSCs, even in the complete absence of cytokine stimulation. H/F-LVs outperform VSV-G-LVs for efficient correction of Fanconi anemia patient cells in unfractionated BM.

Cited by 39 publications

References 76 publications

Efficient and robust NK-Cell transduction with Baboon Envelope pseudotyped lentivector: a major tool for immunotherapy

Efficient and robust NK-Cell transduction with Baboon Envelope pseudotyped lentivector: a major tool for immunotherapy

Lentiviral Vector Pseudotypes: Precious Tools to Improve Gene Modification of Hematopoietic Cells for Research and Gene Therapy

Adenovirus vectors in hematopoietic stem cell genome editing

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