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Article: Protective and Therapeutic Effects of an IL-15:IL-15Rα-Secreting Cell-Based Cancer Vaccine Using a Baculovirus System.

Do-Thi, Van Anh / Lee, Hayyoung / Jeong, Hye Jin / Lee, Jie-Oh / Kim, Young Sang

2021 Volume 13, Issue 16

Abstract: This study reports the use of the BacMam system to deliver and express self-assembling IL-15 and IL-15Rα genes to murine B16F10 melanoma and CT26 colon cancer cells. BacMam-based IL-15 and IL-15Rα were well-expressed and assembled to form the ... ...

Abstract	This study reports the use of the BacMam system to deliver and express self-assembling IL-15 and IL-15Rα genes to murine B16F10 melanoma and CT26 colon cancer cells. BacMam-based IL-15 and IL-15Rα were well-expressed and assembled to form the biologically functional IL-15:IL-15Rα complex. Immunization with this IL-15:IL-15Rα cancer vaccine delayed tumor growth in mice by inducing effector memory CD4
Language	English
Publishing date	2021-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13164039
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Article ; Online: IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines.

Do-Thi, Van Anh / Park, Sang Min / Park, Song Mi / Jeong, Hye Jin / Cho, Geunyoung / An, Hyun-Jung / Kim, Young Sang / Lee, Hayyoung / Lee, Jie-Oh

Cancer research communications

2023 Volume 3, Issue 1, Page(s) 80–96

Abstract: Tumor-associated macrophages (TAM) are involved in tumor progression, metastasis, and immunosuppression. Because TAMs are highly plastic and could alter their phenotypes to proinflammatory M1 in response to environmental stimuli, reeducating TAMs has ... ...

Abstract	Tumor-associated macrophages (TAM) are involved in tumor progression, metastasis, and immunosuppression. Because TAMs are highly plastic and could alter their phenotypes to proinflammatory M1 in response to environmental stimuli, reeducating TAMs has emerged as a promising approach to overcoming the challenges of solid cancer treatment. This study investigated the effect of IL9 on macrophage M1 polarization and verified its antitumor potential to retrain TAMs and promote chemokine secretion. We demonstrated that IL9 stimulated macrophage proliferation and polarized them toward the proinflammatory M1 phenotype in an IFNγ-dependent manner. Tumor-localized IL9 also polarized TAMs toward M1 Significance: These findings clarified the effect of IL9 on macrophage M1 polarization and verified its antitumor potential through retraining TAMs and chemokine secretion.
MeSH term(s)	Mice ; Animals ; Interleukin-9/pharmacology ; Macrophages ; Melanoma/pathology ; Macrophage Activation ; Chemokines/pharmacology ; Tumor Microenvironment
Chemical Substances	Interleukin-9 ; Chemokines
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-22-0246
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Article: Crosstalk between the Producers and Immune Targets of IL-9.

Do-Thi, Van Anh / Lee, Jie-Oh / Lee, Hayyoung / Kim, Young Sang

Immune network

2020 Volume 20, Issue 6, Page(s) e45

Abstract: IL-9 has been reported to play dual roles in the pathogenesis of autoimmune disorders and cancers. The collaboration of IL-9 with microenvironmental factors including the broader cytokine milieu and other cellular components may provide important keys to ...

Abstract	IL-9 has been reported to play dual roles in the pathogenesis of autoimmune disorders and cancers. The collaboration of IL-9 with microenvironmental factors including the broader cytokine milieu and other cellular components may provide important keys to explain its conflicting effects in chronic conditions. In this review, we summarize recent findings on the cellular sources of, and immunological responders to IL-9, in order to interpret the role of IL-9 in the regulation of immune responses. This knowledge will provide new perspectives to improve clinical benefits and limit adverse effects of IL-9 when treating pathologic conditions.
Language	English
Publishing date	2020-11-18
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2536191-0
ISSN	2092-6685 ; 1598-2629
ISSN (online)	2092-6685
ISSN	1598-2629
DOI	10.4110/in.2020.20.e45
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Article ; Online: Interleukin-9 Inhibits Lung Metastasis of Melanoma through Stimulating Anti-Tumor M1 Macrophages.

Park, Sang Min / Do-Thi, Van Anh / Lee, Jie-Oh / Lee, Hayyoung / Kim, Young Sang

Molecules and cells

2019 Volume 43, Issue 5, Page(s) 479–490

Abstract: Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was ... ...

Abstract	Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4
MeSH term(s)	Animals ; Cytokines/metabolism ; Female ; Humans ; Interleukin-9/metabolism ; Lung Neoplasms/immunology ; Lung Neoplasms/secondary ; Lung Neoplasms/therapy ; Macrophage Activation ; Macrophages/immunology ; Melanoma/immunology ; Melanoma/pathology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/pathology ; Th1 Cells/immunology
Chemical Substances	Cytokines ; Interleukin-9
Language	English
Publishing date	2019-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2020.0047
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Article: Ectopically Expressed Membrane-bound Form of IL-9 Exerts Immune-stimulatory Effect on CT26 Colon Carcinoma Cells.

Do Thi, Van Anh / Park, Sang Min / Lee, Hayyoung / Kim, Young Sang

Immune network

2018 Volume 18, Issue 1, Page(s) e12

Abstract: IL-9 is a known T cell growth factor with pleiotropic immunological functions, especially in parasite infection and colitis. However, its role in tumor growth is controversial. In this study, we generated tumor clones expressing the membrane-bound form ... ...

Abstract	IL-9 is a known T cell growth factor with pleiotropic immunological functions, especially in parasite infection and colitis. However, its role in tumor growth is controversial. In this study, we generated tumor clones expressing the membrane-bound form of IL-9 (MB-IL-9) and investigated their influences on immune system. MB-IL-9 tumor clones showed reduced tumorigenicity but shortened survival accompanied with severe body weight loss in mice. MB-IL-9 expression on tumor cells had no effect on cell proliferation or major histocompatibility complex class I expression
Language	English
Publishing date	2018-02-22
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2536191-0
ISSN	2092-6685 ; 1598-2629
ISSN (online)	2092-6685
ISSN	1598-2629
DOI	10.4110/in.2018.18.e12
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Article ; Online: Cell-Based IL-15:IL-15Rα Secreting Vaccine as an Effective Therapy for CT26 Colon Cancer in Mice.

Thi, Van Anh Do / Jeon, Hyung Min / Park, Sang Min / Lee, Hayyoung / Kim, Young Sang

Molecules and cells

2019 Volume 42, Issue 12, Page(s) 869–883

Abstract: Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor ... ...

Abstract	Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancercell vaccine using mitomycin C (MMC)-treated IL-15:IL15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) longterm protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4
MeSH term(s)	Animals ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Cell Line, Tumor ; Colonic Neoplasms/immunology ; Colonic Neoplasms/pathology ; Colonic Neoplasms/prevention & control ; Colonic Neoplasms/therapy ; Female ; Immunologic Memory ; Immunotherapy ; Interleukin-15/genetics ; Interleukin-15/immunology ; Interleukin-15/metabolism ; Interleukin-15 Receptor alpha Subunit/genetics ; Interleukin-15 Receptor alpha Subunit/immunology ; Interleukin-15 Receptor alpha Subunit/metabolism ; Mice ; Mice, Inbred BALB C ; Spleen/immunology ; Survival Analysis ; Xenograft Model Antitumor Assays
Chemical Substances	Cancer Vaccines ; Interleukin-15 ; Interleukin-15 Receptor alpha Subunit
Language	English
Publishing date	2019-11-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2019.0188
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Article: Membrane-bound p35 Subunit of IL-12 on Tumor Cells is Functionally Equivalent to Membrane-bound Heterodimeric Single Chain IL-12 for Induction of Anti-tumor Immunity.

Kim, Hyun-Jin / Park, Sang Min / Lee, Hayyoung / Kim, Young Sang

Immune network

2016 Volume 16, Issue 5, Page(s) 305–310

Abstract: In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone ... ...

Abstract	In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone expressing heterodimeric IL-12 as a single chain (mb-scIL-12 tumor clone). The stimulatory effect of mb-scIL-12 on the proliferation of ConA-activated splenocytes was higher than that of mbIL-12 p35
Language	English
Publishing date	2016-10-25
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2536191-0
ISSN	2092-6685 ; 1598-2629
ISSN (online)	2092-6685
ISSN	1598-2629
DOI	10.4110/in.2016.16.5.305
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Article ; Online: Application of antihelix antibodies in protein structure determination.

Kim, Ji Won / Kim, Songwon / Lee, Haerim / Cho, Geunyoung / Kim, Sun Chang / Lee, Hayyoung / Jin, Mi Sun / Lee, Jie-Oh

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 36, Page(s) 17786–17791

Abstract: Antibodies are indispensable tools in protein engineering and structural biology. Antibodies suitable for structural studies should recognize the 3-dimensional (3D) conformations of target proteins. Generating such antibodies and characterizing their ... ...

Abstract	Antibodies are indispensable tools in protein engineering and structural biology. Antibodies suitable for structural studies should recognize the 3-dimensional (3D) conformations of target proteins. Generating such antibodies and characterizing their complexes with antigens take a significant amount of time and effort. Here, we show that we can expand the application of well-characterized antibodies by "transplanting" the epitopes that they recognize to proteins with completely different structures and sequences. Previously, several antibodies have been shown to recognize the alpha-helical conformation of antigenic peptides. We demonstrate that these antibodies can be made to bind to a variety of unrelated "off-target" proteins by modifying amino acids in the preexisting alpha helices of such proteins. Using X-ray crystallography, we determined the structures of the engineered protein-antibody complexes. All of the antibodies bound to the epitope-transplanted proteins, forming accurately predictable structures. Furthermore, we showed that binding of these antihelix antibodies to the engineered target proteins can modulate their catalytic activities by trapping them in selected functional states. Our method is simple and efficient, and it will have applications in protein X-ray crystallography, electron microscopy, and nanotechnology.
MeSH term(s)	Crystallography, X-Ray ; Epitopes/chemistry ; Humans ; Protein Conformation, alpha-Helical ; Proteins/chemistry ; Single-Chain Antibodies/chemistry
Chemical Substances	Epitopes ; Proteins ; Single-Chain Antibodies
Language	English
Publishing date	2019-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1910080116
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Zs.A 1148: Show issues

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Article ; Online: Higd-1a regulates the proliferation of pancreatic cancer cells through a pERK/p27

An, Hyun-Jung / Ryu, Mihyeun / Jeong, Hye Jin / Kang, Minho / Jeon, Hyung-Min / Lee, Jie-Oh / Kim, Young Sang / Lee, Hayyoung

Cancer letters

2019 Volume 461, Page(s) 78–89

Abstract: Higd-1a/HIMP1-a/HIG1, a mitochondrial inner membrane protein, promotes cell survival under low glucose and hypoxic conditions. We previously reported that it interacts with Opa1, a factor involved in mitochondrial fusion, to regulate mitochondrial ... ...

Abstract	Higd-1a/HIMP1-a/HIG1, a mitochondrial inner membrane protein, promotes cell survival under low glucose and hypoxic conditions. We previously reported that it interacts with Opa1, a factor involved in mitochondrial fusion, to regulate mitochondrial homeostasis. In the present study, we found that depletion of Higd-1a inhibited the proliferation of pancreatic cancer cells in vitro and in mice xenografts. Higd-1a knockdown did not itself lead to cell death but it caused cell cycle arrest through induction of p27
MeSH term(s)	Animals ; Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Cycle Checkpoints ; Cell Movement ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p27/genetics ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; Mice, Nude ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Mitogen-Activated Protein Kinase 3/genetics ; Mitogen-Activated Protein Kinase 3/metabolism ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Phosphorylation ; Prognosis ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Signal Transduction ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
Chemical Substances	Biomarkers, Tumor ; CDKN1B protein, human ; HIGD1A protein, human ; Intracellular Signaling Peptides and Proteins ; Mitochondrial Proteins ; Retinoblastoma Protein ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; MAPK3 protein, human (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24)
Language	English
Publishing date	2019-07-13
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2019.07.007
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Zs.A 1177: Show issues

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Article ; Online: The Membrane-Bound Form of IL-17A Promotes the Growth and Tumorigenicity of Colon Cancer Cells.

Do Thi, Van Anh / Park, Sang Min / Lee, Hayyoung / Kim, Young Sang

Molecules and cells

2016 Volume 39, Issue 7, Page(s) 536–542

Abstract: Interleukin-17A is a member of the IL-17 family, and is known as CTLA8 in the mouse. It is produced by T lymphocytes and NK cells and has proinflammatory roles, inducing cytokine and chemokine production. However, its role in tumor biology remains ... ...

Abstract	Interleukin-17A is a member of the IL-17 family, and is known as CTLA8 in the mouse. It is produced by T lymphocytes and NK cells and has proinflammatory roles, inducing cytokine and chemokine production. However, its role in tumor biology remains controversial. We investigated the effects of locally produced IL-17A by transferring the gene encoding it into CT26 colon cancer cells, either in a secretory or a membrane-bound form. Expression of the membrane-bound form on CT26 cells dramatically enhanced their proliferation in vitro. The enhanced growth was shown to be due to an increased rate of cell cycle progression: after synchronizing cells by adding and withdrawing colcemid, the rate of cell cycle progression in the cells expressing the membrane-bound form of IL-17A was much faster than that of the control cells. Both secretory and membrane-bound IL-17A induced the expression of Sca-1 in the cancer cells. When tumor clones were grafted into syngeneic BALB/c mice, the tumor clones expressing the membrane-bound form IL-17A grew rapidly; those expressing the secretory form also grew faster than the wild type CT26 cells, but slower than the clones expressing the membrane-bound form. These results indicate that IL-17A promotes tumorigenicity by enhancing cell cycle progression. This finding should be considered in treating tumors and immune-related diseases.
Language	English
Publishing date	2016-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2016.0048
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