T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles and Their Applications in Cancer Therapy

Calvo, Vı́ctor; Izquierdo, Manuel

doi:10.3390/cells11050790

Cited by 27 publications

(27 citation statements)

References 159 publications

(423 reference statements)

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“…The current research mainly focuses on immune checkpoint blockade combined with CAR-T cells to influence the immunosuppressive microenvironment [22]. However, reiterating the essence of immune synapse formation, increasing the number of target antigens, promoting the number of infiltrating immune cells, and increasing the formation of immune synapses are crucial to improving the therapeutic effects of T cells [23]. Romidepsin is a relatively safe histone deacetylase inhibitor (HDACi) in clinical settings.…”

Section: Discussionmentioning

confidence: 99%

Romidepsin Enhances the Killing Ability of NKG2D-CAR-T Cells through Enhanced Expression of NKG2DL against Ovarian Cancer Cells

Wang¹,

Lin²,

Yu³

et al. 2022

Clin. Exp. Obstet. Gynecol.

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Background: Upregulating tumor cell targeting antigens and improving the cytotoxicity of chimeric antigen receptor T cell (CAR-T) are expected to facilitate better treatment efficacy for solid cancers represented by ovarian cancer. Methods: Killer cell lectin-like receptor subfamily K member 1 ligands (NKG2DL) are the target antigens for ovarian cancer. NKG2D-CAR-T cells were constructed for NKG2D ligand on the ovarian cancer cell surface. We used flow cytometry to evaluate the expression of NKG2DL on SKOV3 (a human ovarian cancer adenocarcinoma cell line). Innovatively, when combined with romidepsin to treat ovarian cancer cell SKOV3, to evaluate the killing ability of the combined strategy, we verified the cytotoxicity of CAR-T cells by lactate dehydrogenase (LDH) release test and determined the secretion of cytokines by enzyme-linked immuno sorbent assay (ELISA). Results: The results of flow cytometry showed effective activation of the NKG2D-CAR-T cells, and romidepsin treatment resulted in increased expression of NKG2DL on the surface of SKOV3. Cytotoxicity test showed that romidepsin could enhance the killing ability of NKG2D-CAR-T cells against ovarian cancer cells by regulating their NKG2DL expression (p < 0.05). The killing effects and secretion of interferon-γ (IFN-γ) increased synchronously (p < 0.05). Levels of interleukin-2 (IL-2) and Pore-forming protein (PFP) were statistically significant at a low target ratio but programmed cell death protein 1 (PD-1) remained unaffected (p ≥ 0.05). Conclusions: Enhancing the expression of tumor target antigen is a solution to improve the limited application of CAR-T cells in solid cancers.

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Section: Discussionmentioning

confidence: 99%

Romidepsin Enhances the Killing Ability of NKG2D-CAR-T Cells through Enhanced Expression of NKG2DL against Ovarian Cancer Cells

Wang¹,

Lin²,

Yu³

et al. 2022

Clin. Exp. Obstet. Gynecol.

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“…CAR-containing exosomes derived from CAR-T cells are not only safe but also hold potential anti-tumor effects [ 105 ], are expected to solve the above problems, and deserve further attention. The biogenesis and secretion of CAR-T-cell-derived exosomes may be positively modulated by some T lymphocyte activation enhancers (i.e., DGK inhibitors, such as R59949), which may constitute a promising strategy for CAR-T-cell-derived exosome-based immunotherapies [ 106 ].…”

Section: Exosomes and Efficacy Of Hcc Immunotherapymentioning

confidence: 99%

Role of Exosomes in Immunotherapy of Hepatocellular Carcinoma

Tian

Han

Dong

et al. 2022

Cancers

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Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, having a significantly poor prognosis and no sufficiently efficient treatments. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided new therapeutic approaches for HCC patients. Nevertheless, most patients with HCC do not benefit from immunotherapy. Exosomes are biologically active lipid bilayer nano-sized vesicles ranging in size from 30 to 150 nm and can be secreted by almost any cell. In the HCC tumor microenvironment (TME), numerous cells are involved in tumor progression, and exosomes—derived from tumor cells and immune cells—exhibit unique composition profiles and act as intercellular communicators by transporting various substances. Showing the dual characteristics of tumor promotion and suppression, exosomes exert multiple functions in shaping tumor immune responses in the crosstalk between tumor cells and surrounding immune cells, mediating immunotherapy resistance by affecting the PD-1/PD-L1 axis or the anti-tumor function of immune cells in the TME. Targeting exosomes or the application of exosomes as therapies is involved in many aspects of HCC immunotherapies (e.g., ICIs, tumor vaccines, and adoptive cell therapy) and may substantially enhance their efficacy. In this review, we discuss the impact of exosomes on the HCC TME and comprehensively summarize the role of exosomes in immunotherapy resistance and therapeutic application. We also discuss the potential of exosomes as biomarkers for predicting the efficacy of immunotherapy to help clinicians in identifying HCC patients who are amenable to immunotherapies.

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“…For many years, exosomes have been thought to only function as molecular carriers that carry waste from cells; however, it has become clear that EVs affect various biological processes and diseases, including immune responses and cancer [ 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 ]. Nonetheless, it is difficult to identify these exosomes.…”

Section: Ev-mediated Immune Escape Of Cancer Cellsmentioning

confidence: 99%

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

Matsuzaka

Yashiro

2022

IJMS

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Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by delivering their contents, such as nucleic acids, proteins, and lipids, to distant target cells. EVs play a role in the progression of several diseases. In particular, programmed death-ligand 1 (PD-L1) levels in exosomes are associated with cancer progression. Furthermore, exosomes are being used for new drug-delivery systems by modifying their membrane peptides to promote their intracellular transduction via micropinocytosis. In this review, we aim to show that an efficient drug-delivery system and a useful therapeutic strategy can be established by controlling the molecular docking and intracellular translocation of exosomes. We summarise the mechanisms of molecular docking of exosomes, the biological effects of exosomes transmitted into target cells, and the current state of exosomes as drug delivery systems.

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T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles and Their Applications in Cancer Therapy

Cited by 27 publications

References 159 publications

Romidepsin Enhances the Killing Ability of NKG2D-CAR-T Cells through Enhanced Expression of NKG2DL against Ovarian Cancer Cells

Romidepsin Enhances the Killing Ability of NKG2D-CAR-T Cells through Enhanced Expression of NKG2DL against Ovarian Cancer Cells

Role of Exosomes in Immunotherapy of Hepatocellular Carcinoma

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

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