Efficient transduction of murine B lymphocytes and B lymphoma lines by modified adenoviral vectors: enhancement via targeting to FcR and heparan-containing proteins

Li, L; Wickham, TJ; Keegan, AD

doi:10.1038/sj.gt.3301487

Cited by 17 publications

(4 citation statements)

References 33 publications

(45 reference statements)

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“…However, we were unable to generate monoclonal lineages of Pfeiffer cells expressing dCas9 and VP64. In other DLBCL cell lines, lentiviral transduction was inefficient (a known property of B lymphocytes and lymphomas [Li et al, 2001]). We therefore performed CRISPRa screens in the chronic myeloid leukemia (CML) cell line K562, which can be efficiently transduced and cloned.…”

Section: Resultsmentioning

confidence: 99%

A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity

Palmer

Chidley

Sorger

2019

eLife

102

101

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Curative cancer therapies are uncommon and nearly always involve multi-drug combinations developed by experimentation in humans; unfortunately, the mechanistic basis for the success of such combinations has rarely been investigated in detail, obscuring lessons learned. Here, we use isobologram analysis to score pharmacological interaction, and clone tracing and CRISPR screening to measure cross-resistance among the five drugs comprising R-CHOP, a combination therapy that frequently cures Diffuse Large B-Cell Lymphomas. We find that drugs in R-CHOP exhibit very low cross-resistance but not synergistic interaction: together they achieve a greater fractional kill according to the null hypothesis for both the Loewe dose-additivity model and the Bliss effect-independence model. These data provide direct evidence for the 50 year old hypothesis that a curative cancer therapy can be constructed on the basis of independently effective drugs having non-overlapping mechanisms of resistance, without synergistic interaction, which has immediate significance for the design of new drug combinations.

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Section: Resultsmentioning

confidence: 99%

A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity

Palmer

Chidley

Sorger

2019

eLife

102

101

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“…This problem may be overcome ex vivo by using Epstein-Barr virus vectors [22], adeno-associated virus vectors [23], or modified adenoviral vectors [24,25]. Recently, we described a transduction method accomplishing highly efficient adenoviral-mediated gene transfer in lymphoma cells [6].…”

Section: Discussionmentioning

confidence: 99%

Untitled

Ebert

Wilbert

Buttgereit

et al. 2004

Genet Vaccines Ther

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Background: Modulation of the immune system by genetically modified lymphoma cell vaccines is of potential therapeutic value in the treatment of B cell lymphoma. However, the anti-tumor effect of any single immunogene transfer has so far been limited. Combination treatment of recombinant IL-2 and IL-12 has been reported to be synergistic for inducing anti-tumor responses in solid tumors but the potential of IL-2/IL-12 gene modified B cell lymphoma cells has not been explored yet.

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“…One group showed that an Ad5 vector with a polylysine-containing fiber was able to transduce LPS-activated murine B cells and B cell lines (93). Another group found up to 6.5-fold enhancement of binding to B cell lines upon insertion of a CD21 binding sequence into the Ad5 fiber (94).…”

Section: Delivery Methodsmentioning

confidence: 99%

Vector Strategies to Actualize B Cell–Based Gene Therapies

Jeske

Boucher

Curiel

et al. 2021

The Journal of Immunology

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Recent developments in genome editing and delivery systems have opened new possibilities for B cell gene therapy. CRISPR-Cas9 nucleases have been used to introduce transgenes into B cell genomes for subsequent secretion of exogenous therapeutic proteins from plasma cells and to program novel B cell Ag receptor specificities, allowing for the generation of desirable Ab responses that cannot normally be elicited in animal models. Genome modification of B cells or their progenitor, hematopoietic stem cells, could potentially substitute Ab or protein replacement therapies that require multiple injections over the long term. To date, B cell editing using CRISPR-Cas9 has been solely employed in preclinical studies, in which cells are edited ex vivo. In this review, we discuss current B cell engineering efforts and strategies for the eventual safe and economical adoption of modified B cells into the clinic, including in vivo viral delivery of editing reagents to B cells.

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Efficient transduction of murine B lymphocytes and B lymphoma lines by modified adenoviral vectors: enhancement via targeting to FcR and heparan-containing proteins

Cited by 17 publications

References 33 publications

A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity

A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity

Untitled

Vector Strategies to Actualize B Cell–Based Gene Therapies

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