Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles

Shin, Sanghee; Jung, Inseong; Jung, Dokyung; Kim, Christine S.; Kang, Sung-Min; Ryu, Suyeon; Choi, Sung-Jin; Noh, Soojeong; Jeong, Jongwon; Lee, Beom Yong; Park, Jun-Kook; Shin, Jiwon; Cho, Hanchae; Heo, Jin-Seok; Jeong, Youngtae; Choi, Sun Ha; Lee, Shin Yup; Baek, Moon‐Chang; Yea, Kyungmoo

doi:10.1016/j.biomaterials.2022.121765

Cited by 31 publications

(13 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The result of our in vitro experiment was in accordance with their result that the miR-10a-5p and miR-10b-5p are lower in AA-Exo group while miR-128 was highly expressed with decreasing proportion of Treg cells. The miR-375 was considered associated with the CD8 + T cell-mediated immune responses 31 while we found that it was the biggest different up-regulated miRNAs in AA-Exos. The miRNA-486 has been demonstrated to modulating in ammatory responses by target at TNF 21 .…”

Section: Discussionmentioning

confidence: 81%

Impaired Immunosuppressive Effect of Bone Marrow Mesenchymal Stem Cell-derived Exosomes on T cells in Aplastic Anemia

Wang

Huo

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Previous studies haveverified the dysfunction of mesenchymal stem cells (MSCs) for immunoregulation in acquired aplastic anemia (AA) patients. Exosomes derived from MSCs can partially substitute MSCs acting as immune regulator. Dysfunction of exosomes (Exos)derived from AA-MSC (AA-Exos) may play a key role in immunologic dissonance. Method: In this study, CD3+ T cells were collected and cocultured with AA-Exos and exosomes derived from MSC of healthy donors(HD-Exos). The proliferation, differentiation and activation of CD3+ T cells were detected to compare the immunosuppressive effects between AA-Exos and HD-Exos. An immune-mediated murine model of AA was structured to compare the therapeutic effect of AA-Exos and HD-Exos. Furthermore, total RNA including miRNA from exosomes we purified and total RNA of CD3+ T cells were extracted for RNA-seq in order to construct the miRNA–mRNA network for interactions and functional analysis. Results: AA-Exos had impaired inhibition effects on CD3+ T cells in terms of cell proliferation, activation and differentiation compared with exosomes from HD-Exos. HD-Exos other than AA-Exos can rescued the AA mice. Importantly, we found some differentially expressed miRNA involved in immune response, such as miR-199, miR-128 and miR-486. The Gene Ontology analysis of differentially expressed genes (DEGs) revealed involvement of various cellular processes, such as lymphocyte chemotaxis, lymphocyte migration and response to interferon-gamma, etc. The Kyoto Encyclopedia of Genes and Genomes analysis illustrated upregulation of critical pathways associated with T cell function after co-culturing with AA-Exos compared with HD-Exos, such as graft-versus-host disease, Th17 cell differentiation, and JAK-STAT signaling pathway, A miRNA–mRNA network was established to visualize the interaction between them. Conclusion: In summary, AA-Exos had impaired immunosuppressive effect on T cells, less ability to rescue AA mice and differently expressed miRNA profile, which might partly account for the pathogenesis of AA as well as provide a new target of AA treatment.

show abstract

Section: Discussionmentioning

confidence: 81%

Impaired Immunosuppressive Effect of Bone Marrow Mesenchymal Stem Cell-derived Exosomes on T cells in Aplastic Anemia

Wang

Huo

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…[15] This specific cytokine signaling induces cytokinemediated cellular function changes within the cell, reprogramming internal components of EVs. [33] Therefore, EVs derived from our engineered cells with tethered cytokines have distinct characteristics compared to non-engineered EVs. [32] In a study by D. Jung et al, attachment of Interleukin 2 to CD4 + T cells altered the miRNA profile within EVs secreted from the engineered cells, leading to lowered PDÀ L1 expression and small EV secretion by cancer cells and enhancing anticancer effects (Figure 3).…”

Section: Engineering Ev Surface With Mtfpmentioning

confidence: 99%

Exploring Membrane‐tethering Technology for Proteins as a Versatile Tool for Uncovering Novel Disease Targets and Advancing Biotherapeutic Development

Noh

Park

Shin

et al. 2023

Israel Journal of Chemistry

Self Cite

View full text Add to dashboard Cite

Membrane‐tethering technology for proteins (MTFP) is a promising approach for the development of therapeutic agents that display bioactive proteins, such as antibodies and cytokines, on the cell surface, resulting in the induction of autocrine signalling. In this review article, we provide a comprehensive overview of the MTFP, including its basic principles, selection of agonist antibodies and peptides, and the identification of novel functions of natural cytokines. Furthermore, we discuss the potential of increasing the therapeutic efficacy of existing treatments by engineering active proteins to the cell and extracellular vesicle surfaces. We suggest that the MTFP has the potential to maximize efficiency in drug discovery by identifying proteins with regulatory functions and engineering existing treatments. Our review highlights the importance of MTFP in basic research and translational research, and its potential to apply the development of biotherapeutics.

show abstract

“…Extracellular vesicles from immune cells, including macrophages, 21–23 dendritic cells, 24,25 and T cells, 26,27 are also utilized in disease therapy because of their immunomodulation capacity. For instance, T cell-derived EVs carry surface markers and cytokines characteristic of T cell subtypes, facilitating antigen presentation, immune activation, and regulation.…”

Section: Source Of Evsmentioning

confidence: 99%

Recent advances in therapeutic engineered extracellular vesicles

Yao,

Zhang,

Wang

2024

Nanoscale

View full text Add to dashboard Cite

show abstract

Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles

Cited by 31 publications

References 61 publications

Impaired Immunosuppressive Effect of Bone Marrow Mesenchymal Stem Cell-derived Exosomes on T cells in Aplastic Anemia

Impaired Immunosuppressive Effect of Bone Marrow Mesenchymal Stem Cell-derived Exosomes on T cells in Aplastic Anemia

Exploring Membrane‐tethering Technology for Proteins as a Versatile Tool for Uncovering Novel Disease Targets and Advancing Biotherapeutic Development

Recent advances in therapeutic engineered extracellular vesicles

Contact Info

Product

Resources

About