Rapid and efficient nonviral gene delivery of CD154 to primary chronic lymphocytic leukemia cells

Li, L H; Biagi, Ettore; Allen, Cornell; Shivakumar, Rama; Weiss, Jonathan M.; Feller, Stephanie; Yvon, Eric; Fratantoni, Joseph C.; Liu, L N

doi:10.1038/sj.cgt.7700883

Cited by 18 publications

(19 citation statements)

References 49 publications

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“…27 These novel vectors may allow expression of costimulatory molecules such as CD40L or B7 molecules in nondividing tumor B cells such as B-CLL cells to elicit immune responses against gene-modified and unmodified cells. 24,28 Thus, H/F- For personal use only. on May 11, 2018…”

Section: Discussionmentioning

confidence: 99%

Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors

Frecha

Costa

Lévy

et al. 2009

Blood

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Section: Discussionmentioning

confidence: 99%

Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors

Frecha

Costa

Lévy

et al. 2009

Blood

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“…It can be used for DNA transfer in dividing and non-dividing cells. It was successfully used in vaccine preparation from autologous B-CLL tumor cells by CD154 gene delivery [75] . The transgene expression was detected 3 h after electroporation and was maintained after long-term cryopreservation [75] .…”

Section: Electroporationmentioning

confidence: 99%

“…It was successfully used in vaccine preparation from autologous B-CLL tumor cells by CD154 gene delivery [75] . The transgene expression was detected 3 h after electroporation and was maintained after long-term cryopreservation [75] . However, other investigators report that gene transfer by electroporation is transient [76] .…”

Section: Electroporationmentioning

confidence: 99%

Exploitation of stem cell homing for gene delivery

Penn¹,

Khalil

2007

Expert Opinion on Biological Therapy

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Stem cells have been the focus of numerous investigations to treat diseases as far ranging as diabetes, chronic heart failure and multiple sclerosis over the past decade. The process of stem-cell-based repair of acute injury involves homing and engrafting of the stem cell of interest to the site of injury followed by either differentiation of the stem cell to indigenous end-organ cells or liberation of paracrine factors that lead to preservation and/or optimization of organ function. Recognition of the ability of stem cells to home to sites of acute injury suggests that, if appropriately defined and harnessed, stem cell homing could serve as a means of local drug delivery through the infusion of genetically engineering stem cells that secrete gene products of interest. The authors have recently demonstrated the use of this approach in preclinical studies of acute myocardial function. In addition, the use of engineered cells that home to appropriate niches have been used to correct genetic deficiency states (i.e., severe combined immunodeficiency, diabetes mellitus) in patients with otherwise chronic debilitating diseases. This review focuses on exploiting stem cell homing for gene transfer and on the state of the art and the challenges that face the field.

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“…Ex vivo modified B cells can produce antibodies against tumor antigens and initiate antibody-mediated cell death. B cell derived cancers can also be more effectively targeted by monoclonal antibodies when target receptors are expressed by modified B cells [5–9]. …”

Section: Introductionmentioning

confidence: 99%

High Efficiency Ex Vivo Gene Transfer to Primary Murine B Cells Using Plasmid or Viral Vectors

Moeini¹,

Zolotukhin²,

Sack³

et al. 2011

J Genet Syndr Gene Ther

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Primary autologous B-lymphocytes, following ex vivo gene transfer and re-implantation, have been successfully utilized to prevent autoimmune disease and adaptive responses to therapeutic proteins in several animal models. However, efficient gene transfer to primary B cells requires use of retroviral vectors, which increase the risk of insertional mutagenesis. Here, we evaluated several alternative gene transfer approaches. Resting splenic B cells were purified and activated with LPS, and ex vivo GFP gene transfer was performed by means of nucleofection, lipofectamine, adenoviral infection, or murine retroviral infection. The Adenoviral (Ad) vectors were added to B cell cultures with or without calcium phosphate precipitation. For transfection and nucleofection, naked plasmid DNA was utilized. Nucleofection technology represents a modified electroporation technique for effective transfer of nucleic acids to the nucleus and thus enhances the efficiency of transfer particularly for primary cells. Efficiency of ex vivo gene transfer was determined by flow cytometry using GFP, CD19, and a vital dye as markers. Nucleofection yielded the highest level of gene transfer with 60–65% of B cells being GFP+. Efficiencies were 30–35% for retrovirus, 20% for Ad5/11, 15% for Ad5/35, and 5% for lipofectamine-mediated transfection. Calcium phosphate precipitation increased efficiencies for Ad vectors to 30% (Ad5/11) and 25% (Ad5/35). Lipofectamin caused the greatest cell death at 80%, followed by nucleofection (35%), and viral vector (10–15% in each case). For all methods, gene transfer efficiencies were nearly identical for B cells from C57BL/6 or C3H/HeOuJ mice. In conclusion, recent advances in gene transfer technologies provide alternatives to retroviral vectors for primary B cells. If stable gene transfer is desired, non-integrating vector systems may be combined with transposon- or phage integrase-based systems or future site-specific systems to achieve integration into the host B cell genome.

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Rapid and efficient nonviral gene delivery of CD154 to primary chronic lymphocytic leukemia cells

Cited by 18 publications

References 49 publications

Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors

Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors

Exploitation of stem cell homing for gene delivery

High Efficiency Ex Vivo Gene Transfer to Primary Murine B Cells Using Plasmid or Viral Vectors

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