Biological Function and Immunotherapy Utilizing Phosphatidylserine-based Nanoparticles

Glassman, Fiona Y.; Dingman, Robert; Yau, Helena C; Balu‐Iyer, Sathy V.

doi:10.1080/08820139.2020.1738456

Cited by 9 publications

(4 citation statements)

References 93 publications

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“…Since particle size is a critical parameter that influences receptor binding, lymphatic uptake, cellular interaction, and pharmacokinetics of drug delivery system [27][28][29][30][31] , we performed a size analysis of DMPC multilamellar vesicles (MLVs) containing increasing concentrations of 18:1 Lyso-PS using the DLS approach. The inclusion of Lyso-PS into DMPC bilayers significantly reduced the particles' hydrodynamic diameter in a concentration-dependent manner, with the greatest reduction observed at 30 mol% of Lyso-PS (Fig.…”

Section: Effect Of Lyso-ps On the Particle Size Of Dmpc Vesiclesmentioning

confidence: 99%

Biophysical Characterization of Tolerogenic Lipid-Based Nanoparticles Containing Phosphatidylcholine and Lysophosphatidylserine

Nguyen¹,

Chen²,

Chak

et al. 2022

Journal of Pharmaceutical Sciences

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Effect Of Lyso-ps On the Particle Size Of Dmpc Vesiclesmentioning

confidence: 99%

Biophysical Characterization of Tolerogenic Lipid-Based Nanoparticles Containing Phosphatidylcholine and Lysophosphatidylserine

Nguyen¹,

Chen²,

Chak

et al. 2022

Journal of Pharmaceutical Sciences

Self Cite

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“…Similarly, engagement of TIM-3 by the carbohydrate Galectin-9 [ 375 ], generated by various cell types [ 381 , 382 , 383 , 384 ], induced Th1 effector cell apoptosis [ 375 ]. On the contrary, binding of TIM-3 to PS [ 385 ], characteristic for apoptotic cells [ 386 ], enhanced T-cell activity [ 387 ]. With regard to other cell types, TIM-3/Galectin-9 ligation was reported to either promote DC [ 388 ] and NK cell [ 389 ] activity, and to favor expansion of DCs and NKT cells [ 390 ].…”

Section: Emerging Immune Checkpoints and Their Impact On Non-t-cell I...mentioning

confidence: 99%

Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses?

Kuske

Haist

Jung

et al. 2022

Cancers

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The approval of immune checkpoint inhibitors (ICI) that serve to enhance effector T-cell anti-tumor responses has strongly improved success rates in the treatment of metastatic melanoma and other tumor types. The currently approved ICI constitute monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein (CTLA)-4 and anti-programmed cell death (PD)-1. By this, the T-cell-inhibitory CTLA-4/CD80/86 and PD-1/PD-1L/2L signaling axes are inhibited. This leads to sustained effector T-cell activity and circumvents the immune evasion of tumor cells, which frequently upregulate PD-L1 expression and modulate immune checkpoint molecule expression on leukocytes. As a result, profound clinical responses are observed in 40–60% of metastatic melanoma patients. Despite the pivotal role of T effector cells for triggering anti-tumor immunity, mounting evidence indicates that ICI efficacy may also be attributable to other cell types than T effector cells. In particular, emerging research has shown that ICI also impacts innate immune cells, such as myeloid cells, natural killer cells and innate lymphoid cells, which may amplify tumoricidal functions beyond triggering T effector cells, and thus improves clinical efficacy. Effects of ICI on non-T cells may additionally explain, in part, the character and extent of adverse effects associated with treatment. Deeper knowledge of these effects is required to further develop ICI treatment in terms of responsiveness of patients to treatment, to overcome resistance to ICI and to alleviate adverse effects. In this review we give an overview into the currently known immunomodulatory effects of ICI treatment in immune cell types other than the T cell compartment.

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“…However, PS is expressed on the surface of apoptotic cells as well as non-apoptotic cancer cells such as malignant melanoma, leukemia, neuroblastoma and gastric carcinoma [76]. The immunosuppressive effects of PS are well documented [73] and are being utilized to suppress unwanted immune responses in several diseases [77][78][79]. PS binds to a variety of different receptors on immune cells [73].…”

Section: Immunosuppressive Lipids Associated With Tumor Exosomesmentioning

confidence: 99%

Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments

Shenoy

Bhatta

Bankert

2021

Cells

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Exosomes are a subset of extracellular vesicles (EVs) that are released by cells and play a variety of physiological roles including regulation of the immune system. Exosomes are heterogeneous and present in vast numbers in tumor microenvironments. A large subset of these vesicles has been demonstrated to be immunosuppressive. In this review, we focus on the suppression of T cell function by exosomes in human tumor microenvironments. We start with a brief introduction to exosomes, with emphasis on their biogenesis, isolation and characterization. Next, we discuss the immunosuppressive effect of exosomes on T cells, reviewing in vitro studies demonstrating the role of different proteins, nucleic acids and lipids known to be associated with exosome-mediated suppression of T cell function. Here, we also discuss initial proof-of-principle studies that established the potential for rescuing T cell function by blocking or targeting exosomes. In the final section, we review different in vivo models that were utilized to study as well as target exosome-mediated immunosuppression, highlighting the Xenomimetic mouse (X-mouse) model and the Omental Tumor Xenograft (OTX) model that were featured in a recent study to evaluate the efficacy of a novel phosphatidylserine-binding molecule for targeting immunosuppressive tumor-associated exosomes.

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Biological Function and Immunotherapy Utilizing Phosphatidylserine-based Nanoparticles

Cited by 9 publications

References 93 publications

Biophysical Characterization of Tolerogenic Lipid-Based Nanoparticles Containing Phosphatidylcholine and Lysophosphatidylserine

Biophysical Characterization of Tolerogenic Lipid-Based Nanoparticles Containing Phosphatidylcholine and Lysophosphatidylserine

Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses?

Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments

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