Programming Cell-Cell Interactions through Non-genetic Membrane Engineering

Csizmar, Clifford M.; Petersburg, Jacob; Wagner, Carston R.

doi:10.1016/j.chembiol.2018.05.009

Cited by 73 publications

(74 citation statements)

References 66 publications

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“…Drug delivery strategies for cellular engineering, from gene editing to nanoparticle and lipid carriers, are under continuous and rapid development (1,2,61). For example, nanoparticles have been used in multiple formulations to boost cellular therapies by delivering drugs with immune cells in vivo (62)(63)(64).…”

Section: Discussionmentioning

confidence: 99%

“…In cell-based immunotherapy, drugs are administered systemically to target immune cells in vivo, or carried by ex vivo-primed autologous immune cells that are reinfused into patients. Strategies to engineer cells as drug-carriers ex vivo include genome editing, conjugating biomaterial-based carriers to cell surfaces, and binding of the plasma membrane for passive diffusion of immunostimulatory ligands (1,2). Despite successful implementation in the clinic, cell-based immunotherapies still face challenges of implementing simple and efficient delivery that improve therapeutic responses.…”

Section: Introductionmentioning

confidence: 99%

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Lipid-Mediated Insertion of Toll-Like Receptor (TLR) Ligands for Facile Immune Cell Engineering

et al. 2020

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Cell-based immunotherapies have tremendous potential to treat many diseases, such as activating immunity in cancer or suppressing it in autoimmune diseases. Most cell-based cancer immunotherapies in the clinic provide adjuvant signals through genetic engineering to enhance T cell functions. However, genetically encoded signals have minimal control over dosing and persist for the life of a cell lineage. These properties make it difficult to balance increasing therapeutic efficacy with reducing toxicities. Here, we demonstrated the potential of phospholipid-coupled ligands as a non-genetic system for immune cell engineering. This system provides simple, controlled, non-genetic adjuvant delivery to immune cells via lipid-mediated insertion into plasma membranes. Lipid-mediated insertion (termed depoting) successfully delivered Toll-like receptor (TLR) ligands intracellularly and onto cell surfaces of diverse immune cells. These ligands depoted into immune cells in a dose-controlled fashion and did not compete during multiplex pairwise loading. Immune cell activation could be enhanced by autocrine and paracrine mechanisms depending on the biology of the TLR ligand tested. Depoted ligands functionally persisted on plasma membranes for up to 4 days in naïve and activated T cells, enhancing their activation, proliferation, and skewing cytokine secretion. Our data showed that depoted ligands provided a persistent yet non-permanent adjuvant signal to immune cells that may minimize the intensity and duration of toxicities compared to permanent genetic delivery. Altogether, these findings demonstrate potential for lipid-mediated depoting as a universal cell engineering approach with unique, complementary advantages to other cell engineering methods.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid-Mediated Insertion of Toll-Like Receptor (TLR) Ligands for Facile Immune Cell Engineering

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Drug delivery strategies for cellular engineering, from gene editing to nanoparticle and lipid carriers, are under continuous and rapid development (2,57,58). For example, nanoparticles have been used in multiple formulations to boost cellular therapies by delivering drugs with immune cells in vivo (59)(60)(61).…”

Section: Discussionmentioning

confidence: 99%

Lipid-mediated insertion of Toll-like receptor (TLR) ligands for facile immune cell engineering

Zhang

Slaby

Stephanie

et al. 2019

Preprint

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AbstractCell-based immunotherapies have tremendous potential to treat many diseases, such as activating immunity in cancer or suppressing it in autoimmune diseases. Most cell-based cancer immunotherapies in the clinic provide adjuvant signals through genetic engineering to enhance T cell functions. However, genetically encoded signals have minimal control over dosing and persist for the life of a cell lineage. These properties make it difficult to balance increasing therapeutic efficacy with reducing toxicities. Here, we demonstrated the potential of phospholipid-coupled ligands as a non-genetic system for immune cell engineering. This system provides simple, controlled, non-genetic adjuvant delivery to immune cells via lipid-mediated insertion into plasma membranes. Lipid-mediated insertion (depoting) successfully delivered Toll-like receptor (TLR) ligands intracellularly and onto cell surfaces of diverse immune cells. These ligands depoted into immune cells in a dose-controlled fashion and did not compete during multiplex pairwise loading. Immune cell activation could be enhanced by autocrine and paracrine mechanisms depending on the biology of the TLR ligand tested. We determined that depoted ligands can functionally persist on plasma membranes for up to four days in naïve and activated T cells, enhancing their activation, proliferation, and skewing cytokine secretion. Depoted ligands provide a persistent yet non-permanent adjuvant signal to immune cells that may minimize the intensity and duration of toxicities compared to permanent genetic delivery. Altogether, these findings demonstrate potential for lipid-mediated insertion (depoting) as a universal cell engineering approach with unique, complementary advantages to other cell engineering methods.

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“…Non-genetic cell surface engineering can be broadly divided into covalent chemical conjugation and noncovalent physical bioconjugation. Those different non-genetic cell surface engineering strategies are summarized in many recent reviews [10,19,25,26,[31][32][33][34][35]. Among these, the non-genetic cell surface engineering that is used to modulate and investigate cell functions and control cell-cell and cell-microenvironment interactions can be found in previous review articles [29,32,34].…”

Section: Introductionmentioning

confidence: 99%

“…Those different non-genetic cell surface engineering strategies are summarized in many recent reviews [10,19,25,26,[31][32][33][34][35]. Among these, the non-genetic cell surface engineering that is used to modulate and investigate cell functions and control cell-cell and cell-microenvironment interactions can be found in previous review articles [29,32,34]. The application of non-genetic cell surface engineering to improve the therapeutic potential of whole-cell-based therapeutics has been reviewed previously [10,19,26,31].…”

Section: Introductionmentioning

confidence: 99%

Advances on Non-Genetic Cell Membrane Engineering for Biomedical Applications

Liu

2019

Polymers

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Cell-based therapeutics are very promising modalities to address many unmet medical needs, including genetic engineering, drug delivery, and regenerative medicine as well as bioimaging. To enhance the function and improve the efficacy of cell-based therapeutics, a variety of cell surface engineering strategies (genetic engineering and non-genetic engineering) are developed to modify the surface of cells or cell-based therapeutics with some therapeutic molecules, artificial receptors, and multifunctional nanomaterials. In comparison to complicated procedures and potential toxicities associated with genetic engineering, non-genetic engineering strategies have emerged as a powerful and compatible complement to traditional genetic engineering strategies for enhancing the function of cells or cell-based therapeutics. In this review, we will first briefly summarize key non-genetic methodologies including covalent chemical conjugation (surface reactive groups–direct conjugation, and enzymatically mediated and metabolically mediated indirect conjugation) and noncovalent physical bioconjugation (biotinylation, electrostatic interaction, and lipid membrane fusion as well as hydrophobic insertion), which have been developed to engineer the surface of cell-based therapeutics with various materials. Next, we will comprehensively highlight the latest advances in non-genetic cell membrane engineering surrounding different cells or cell-based therapeutics, including whole-cell-based therapeutics, cell membrane-derived therapeutics, and extracellular vesicles. Advances will be focused specifically on cells that are the most popular types in this field, including erythrocytes, platelets, cancer cells, leukocytes, stem cells, and bacteria. Finally, we will end with the challenges, future trends, and our perspectives of this relatively new and fast-developing research field.

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Programming Cell-Cell Interactions through Non-genetic Membrane Engineering

Cited by 73 publications

References 66 publications

Lipid-Mediated Insertion of Toll-Like Receptor (TLR) Ligands for Facile Immune Cell Engineering

Lipid-Mediated Insertion of Toll-Like Receptor (TLR) Ligands for Facile Immune Cell Engineering

Lipid-mediated insertion of Toll-like receptor (TLR) ligands for facile immune cell engineering

Advances on Non-Genetic Cell Membrane Engineering for Biomedical Applications

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