Non-viral transfection technologies for next-generation therapeutic T cell engineering

Raes, Laurens; Smedt, Stefaan C. De; Raemdonck, Koen; Braeckmans, Kevin

doi:10.1016/j.biotechadv.2021.107760

Cited by 38 publications

(32 citation statements)

References 271 publications

(375 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these delivery methods, one of the most advanced is electroporation. [55][56][57] Here, cells are typically coincubated with the cargo of interest in a conducting buffer solution within a dielectric chamber with parallel plate electrodes.…”

Section: Keynote (Green) Tablementioning

confidence: 99%

“…as indirect labeling relies on genetic engineering, which is cur-524 rently achieved through viral delivery, it is associated with a high 525 regulatory burden. 56,122,123 Although ACTs such as CAR-T cells 526 already apply ex vivo genetic engineering, the requirement to payload capacities could help to overcome these barriers, but will require alternative intracellular delivery methods (such as electroporation) for crossing the cell membrane. 122 Finally, the introduction of exogenous reporter genes into the T cell genome carries an additional risk of toxicity or immunogenicity, which requires detailed investigation before clinical application can be considered.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Non-invasive cell-tracking methods for adoptive T cell therapies

Hoeck

Vanhove

Smedt

et al. 2022

Drug Discovery Today

Self Cite

View full text Add to dashboard Cite

Section: Keynote (Green) Tablementioning

confidence: 99%

mentioning

confidence: 99%

Non-invasive cell-tracking methods for adoptive T cell therapies

Hoeck

Vanhove

Smedt

et al. 2022

Drug Discovery Today

Self Cite

View full text Add to dashboard Cite

“…Furthermore, chimeric antigen receptor (CAR)-redirected T cells have been proven to be efficacious in the treatment of hematologic malignancy; however, CAR-redirected T cells showed less capacity to eliminate solid tumors due to the barrier of the TME. As such, MSCs can be used to generate “tracks” and guide CAR-T cells into the tumor site while continually secreting supporting factors to maintain the activity of CAR-T cells [ 179 ].…”

Section: Perspectivesmentioning

confidence: 99%

Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy

et al. 2021

View full text Add to dashboard Cite

Due to their “tumor homing” and “immune privilege” characteristics, the use of mesenchymal stem cells (MSCs) has been proposed as a novel tool against cancer. MSCs are genetically engineered in vitro and then utilized to deliver tumoricidal agents, including prodrugs and bioactive molecules, to tumors. The genetic modification of MSCs can be achieved by various vectors, and in most cases viral vectors are used; however, viruses may be associated with carcinogenesis and immunogenicity, restricting their clinical translational potential. As such, nonviral vectors have emerged as a potential solution to address these limitations and have gradually attracted increasing attention. In this review, we briefly revisit the current knowledge about MSC-based cancer gene therapy. Then, we summarize the advantages and challenges of nonviral vectors for MSC transfection. Finally, we discuss recent advances in the development of new nonviral vectors, which have provided promising strategies to overcome obstacles in the gene modulation of MSCs.

show abstract

“…Integrating viral-based gene delivery tools composed of either gammaretrovirus or lentivirus backbones are typically used to generate CAR T cells [ 130 ]. Although gammaretroviruses are stable and yield high viral titres, they can only carry relatively small gene constructs.…”

Section: Engineering Techniques For Delivering Polycistronic Gene Constructsmentioning

confidence: 99%

Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment

Fowler

Nattress

Navarrete

et al. 2021

Cancers

View full text Add to dashboard Cite

Although chimeric antigen receptor (CAR) T cells have shown impressive clinical success against haematological malignancies such as B cell lymphoma and acute lymphoblastic leukaemia, their efficacy against non-haematological solid malignancies has been largely disappointing. Solid tumours pose many additional challenges for CAR T cells that have severely blunted their potency, including homing to the sites of disease, survival and persistence within the adverse conditions of the tumour microenvironment, and above all, the highly immunosuppressive nature of the tumour milieu. Gene engineering approaches for generating immune cells capable of overcoming these hurdles remain an unmet therapeutic need and ongoing area of research. Recent advances have involved gene constructs for membrane-bound and/or secretable proteins that provide added effector cell function over and above the benefits of classical CAR-mediated cytotoxicity, rendering immune cells not only as direct cytotoxic effectors against tumours, but also as vessels for payload delivery capable of both modulating the tumour microenvironment and orchestrating innate and adaptive anti-tumour immunity. We discuss here the novel concept of engineered immune cells as vessels for payload delivery into the tumour microenvironment, how these cells are better adapted to overcome the challenges faced in a solid tumour, and importantly, the novel gene engineering approaches required to deliver these more complex polycistronic gene constructs.

show abstract

Non-viral transfection technologies for next-generation therapeutic T cell engineering

Cited by 38 publications

References 271 publications

Non-invasive cell-tracking methods for adoptive T cell therapies

Non-invasive cell-tracking methods for adoptive T cell therapies

Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy

Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment

Contact Info

Product

Resources

About