Glycosyl-Phosphatidylinositol-Anchored Interleukin-2 Expressed on Tumor-Derived Exosomes Induces Antitumor Immune Response in Vitro

Zhang, Jia-Mo; Zhang, Yao; Luo, Chunli; Xia, Yuguo; Chen, Honglin; Wu, Xiaohou

doi:10.1177/030089161009600313

Cited by 21 publications

(11 citation statements)

References 31 publications

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“…In immunotherapy, by ensuring the transmission of signals from CD4+ T cells to CD8+ T cells and regulating the metabolic activities of T cells, the CTL response can be optimized, which may enhance anti-cancer immunity [36]. In renal cancer, exosomes derived from glycolipidanchored-IL-12 (GPI-IL-12) gene-modified tumor cells express the tumor-associated antigen MAGE-1 and tumor rejection antigens G250 and GPI-IL-12, which significantly promote T cell proliferation and increase interferon (IFN)-γ in turn, and efficiently trigger a stronger activity of CTLs through the FasL/Fas signaling pathway [37,38]. Breast cancer exosomes inhibit both CD8+ and CD4+ T cell proliferation by initiating cell apoptosis and suppressing NK cell cytotoxicity and, hence, may inhibit the anticancer immune response [39].…”

Section: Tumor-released Exosomesmentioning

confidence: 99%

Exosome-based immunotherapy: a promising approach for cancer treatment

et al. 2020

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In the era of the rapid development of cancer immunotherapy, there is a high level of interest in the application of cell-released small vesicles that stimulate the immune system. As cell-derived nanovesicles, exosomes show great promise in cancer immunotherapy because of their immunogenicity and molecular transfer function. The cargoes carried on exosomes have been recently identified with improved technological advances and play functional roles in the regulation of immune responses. In particular, exosomes derived from tumor cells and immune cells exhibit unique composition profiles that are directly involved in anticancer immunotherapy. More importantly, exosomes can deliver their cargoes to targeted cells and thus influence the phenotype and immune-regulation functions of targeted cells. Accumulating evidence over the last decade has further revealed that exosomes can participate in multiple cellular processes contributing to cancer development and therapeutic effects, showing the dual characteristics of promoting and suppressing cancer. The potential of exosomes in the field of cancer immunotherapy is huge, and exosomes may become the most effective cancer vaccines, as well as targeted antigen/drug carriers. Understanding how exosomes can be utilized in immune therapy is important for controlling cancer progression; additionally, exosomes have implications for diagnostics and the development of novel therapeutic strategies. This review discusses the role of exosomes in immunotherapy as carriers to stimulate an anti-cancer immune response and as predictive markers for immune activation; furthermore, it summarizes the mechanism and clinical application prospects of exosome-based immunotherapy in human cancer.

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Section: Tumor-released Exosomesmentioning

confidence: 99%

Exosome-based immunotherapy: a promising approach for cancer treatment

et al. 2020

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“…To perhaps better ensure membrane expression of IL2, T24 human bladder cancer cells (expressing the tumor antigen MAGE1) were transfected with a construct that linked IL2 to a glycosyl-phosphatidylinositol (GPI) anchor resulting in membrane display on the cells and apparently on the TEX as well. These GPI-IL2 TEX stimulated DCs more efficiently to generate specific CTL responses against T24 cells in vivo [ 116 ].…”

Section: Tex As Anti-cancer Vaccinesmentioning

confidence: 99%

The Dichotomy of Tumor Exosomes (TEX) in Cancer Immunity: Is It All in the ConTEXt?

Kunigelis

Graner

2015

Vaccines

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Exosomes are virus-sized nanoparticles (30–130 nm) formed intracellularly as intravesicular bodies/intralumenal vesicles within maturing endosomes (“multivesicular bodies”, MVBs). If MVBs fuse with the cell’s plasma membrane, the interior vesicles may be released extracellularly, and are termed “exosomes”. The protein cargo of exosomes consists of cytosolic, membrane, and extracellular proteins, along with membrane-derived lipids, and an extraordinary variety of nucleic acids. As such, exosomes reflect the status and identity of the parent cell, and are considered as tiny cellular surrogates. Because of this closely entwined relationship between exosome content and the source/status of the parental cell, conceivably exosomes could be used as vaccines against various pathologies, as they contain antigens associated with a given disease, e.g., cancer. Tumor-derived exosomes (TEX) have been shown to be potent anticancer vaccines in animal models, driving antigen-specific T and B cell responses, but much recent literature concerning TEX strongly places the vesicles as powerfully immunosuppressive. This dichotomy suggests that the context in which the immune system encounters TEX is critical in determining immune stimulation versus immunosuppression. Here, we review literature on both sides of this immune coin, and suggest that it may be time to revisit the concept of TEX as anticancer vaccines in clinical settings.

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“…Bone marrow cells from the C57BL/6 mice were cultured in RPMI-1640 medium containing 10% FCS, 10 ng/ml granulocyte macrophage-colony stimulating factor and 1 ng/ml IL-4 to generate bone marrow-derived DCs (BMDCs). Following culture growth for a period of five days, 1x10 6 /ml BMDCs were stimulated with 1 or 10 µg/ml CD40L-EXO, LacZ-EXO and Control-EXO or 1 µg/ml lipopolysaccharide (LPS) for 48 h. For FACS analysis of the BMDCs, 1x10 6 BMDCs were incubated with the corresponding PE-conjugated antibodies for 20 min.…”

Section: Generation and Fluorescence-activated Cell Sorting (Facs)mentioning

confidence: 99%

“…Exosomes may be released from various living cells, including tumor cells, dendritic cells (DCs), platelets, cytotoxic T lymphocytes (CTLs) and reticulocytes (2,5). Exosomes derived from tumor cells (TEX) contain tumor antigens, and a number of studies have indicated that exosomes may be used as an effective vaccine to initiate antitumor immunity (6,7). However, the immunogenicity of the tumor antigen in TEX is poor and the efficiency of TEX to induce antitumor immunity requires further improvement.…”

Section: Introductionmentioning

confidence: 99%

More efficient induction of antitumor T cell immunity by exosomes from CD40L gene-modified lung tumor cells

Wang

Lin

et al. 2013

Molecular Medicine Reports

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The incidence of lung cancer increases annually. However, the effects of the present methods for the treatment of lung cancer are extremely poor. It has been reported that exosomes from heat‑stressed 3LL Lewis lung tumor cells effectively elicit systemic antitumor immunity. CD40 signaling is critical in the activation of dendritic cells (DCs), which are important in the induction of antitumor immunity. In the present study, exosomes from CD40 ligand gene‑modified 3LL tumor cells (CD40L‑EXO) were identified to be more immunogenic compared with control‑EXO and lac Z-EXO. CD40L‑EXO induced a more mature phenotype of the DCs and promoted them to secrete high levels of interleukin‑12. CD40L‑EXO‑treated DCs induced a greater proliferation of allogeneic T cells in the mixed lymphocyte reaction. Moreover, CD40L‑EXO induced robust tumor antigen‑specific CD4+ T cell proliferation ex vivo. CD40L‑EXO were also extremely effective in the protective and therapeutic antitumor tests in vivo. These results indicate that CD40L‑EXO may be used as an efficient vaccine for lung cancer immunotherapy.

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Glycosyl-Phosphatidylinositol-Anchored Interleukin-2 Expressed on Tumor-Derived Exosomes Induces Antitumor Immune Response in Vitro

Abstract: GPI-IL-2 gene-modified tumor cells can make the TEXs contain GPI-IL-2, resulting in increased antitumor effects. Our study provided a feasible approach for exosome-based tumor immunotherapy.

Cited by 21 publications

References 31 publications

Exosome-based immunotherapy: a promising approach for cancer treatment

Exosome-based immunotherapy: a promising approach for cancer treatment

The Dichotomy of Tumor Exosomes (TEX) in Cancer Immunity: Is It All in the ConTEXt?

More efficient induction of antitumor T cell immunity by exosomes from CD40L gene-modified lung tumor cells

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