Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand.
Although dendritic cell (DC)-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in do...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5708771?pdf=render |
| _version_ | 1818422796187860992 |
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| author | Nadeeka H De Silva Takashi Akazawa Viskam Wijewardana Norimitsu Inoue Maremichi Oyamada Atsuko Ohta Yuki Tachibana Daluthgamage Patsy H Wijesekera Mitsuru Kuwamura Yasuko Nishizawa Kazuyuki Itoh Takeshi Izawa Shingo Hatoya Tetsuya Hasegawa Jyoji Yamate Toshio Inaba Kikuya Sugiura |
| author_facet | Nadeeka H De Silva Takashi Akazawa Viskam Wijewardana Norimitsu Inoue Maremichi Oyamada Atsuko Ohta Yuki Tachibana Daluthgamage Patsy H Wijesekera Mitsuru Kuwamura Yasuko Nishizawa Kazuyuki Itoh Takeshi Izawa Shingo Hatoya Tetsuya Hasegawa Jyoji Yamate Toshio Inaba Kikuya Sugiura |
| author_sort | Nadeeka H De Silva |
| collection | DOAJ |
| description | Although dendritic cell (DC)-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in dogs. However, improvement was necessary to be effective to largely developed or metastatic tumors. To obtain effective methods applicable to those tumors, we herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the therapeutic effects in murine subcutaneous and visceral tumor models and also in the clinical treatment of canine cancers. In murine experiments, most and significant inhibition of tumor growth and extended survival was observed in the group treated with the combination of h11c-activated DCs in combination with interferon-gamma and a cyclooxygenase2 inhibitor. Both monocytic and granulocytic myeloid-derived suppressor cells were significantly reduced by the combined treatment. Following the successful results in mice, the combined treatment was examined against canine cancers, which spontaneously generated like as those in human. The combined treatment elicited significant clinical responses against a nonepithelial malignant tumor and a malignant fibrous histiocytoma. The treatment was also successful against a bone-metastasis of squamous cell carcinoma. In the successful cases, the marked increase of tumor-responding T cells and decrease of myeloid-derived suppressor cells and regulatory T cells was observed in their peripheral blood. Although the combined treatment permitted the growth of lung cancer of renal carcinoma-metastasis, the marked elevated and long-term maintaining of the tumor-responding T cells was observed in the patient dog. Overall, the combined treatment gave rise to emphatic amelioration in DC-based cancer therapy. |
| first_indexed | 2024-12-14T13:31:57Z |
| format | Article |
| id | doaj.art-1d3dc6a1bf854751b06088d606d6cb0e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T13:31:57Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1d3dc6a1bf854751b06088d606d6cb0e2022-12-21T22:59:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011211e018873810.1371/journal.pone.0188738Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand.Nadeeka H De SilvaTakashi AkazawaViskam WijewardanaNorimitsu InoueMaremichi OyamadaAtsuko OhtaYuki TachibanaDaluthgamage Patsy H WijesekeraMitsuru KuwamuraYasuko NishizawaKazuyuki ItohTakeshi IzawaShingo HatoyaTetsuya HasegawaJyoji YamateToshio InabaKikuya SugiuraAlthough dendritic cell (DC)-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in dogs. However, improvement was necessary to be effective to largely developed or metastatic tumors. To obtain effective methods applicable to those tumors, we herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the therapeutic effects in murine subcutaneous and visceral tumor models and also in the clinical treatment of canine cancers. In murine experiments, most and significant inhibition of tumor growth and extended survival was observed in the group treated with the combination of h11c-activated DCs in combination with interferon-gamma and a cyclooxygenase2 inhibitor. Both monocytic and granulocytic myeloid-derived suppressor cells were significantly reduced by the combined treatment. Following the successful results in mice, the combined treatment was examined against canine cancers, which spontaneously generated like as those in human. The combined treatment elicited significant clinical responses against a nonepithelial malignant tumor and a malignant fibrous histiocytoma. The treatment was also successful against a bone-metastasis of squamous cell carcinoma. In the successful cases, the marked increase of tumor-responding T cells and decrease of myeloid-derived suppressor cells and regulatory T cells was observed in their peripheral blood. Although the combined treatment permitted the growth of lung cancer of renal carcinoma-metastasis, the marked elevated and long-term maintaining of the tumor-responding T cells was observed in the patient dog. Overall, the combined treatment gave rise to emphatic amelioration in DC-based cancer therapy.http://europepmc.org/articles/PMC5708771?pdf=render |
| spellingShingle | Nadeeka H De Silva Takashi Akazawa Viskam Wijewardana Norimitsu Inoue Maremichi Oyamada Atsuko Ohta Yuki Tachibana Daluthgamage Patsy H Wijesekera Mitsuru Kuwamura Yasuko Nishizawa Kazuyuki Itoh Takeshi Izawa Shingo Hatoya Tetsuya Hasegawa Jyoji Yamate Toshio Inaba Kikuya Sugiura Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand. PLoS ONE |
| title | Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand. |
| title_full | Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand. |
| title_fullStr | Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand. |
| title_full_unstemmed | Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand. |
| title_short | Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand. |
| title_sort | development of effective tumor immunotherapy using a novel dendritic cell targeting toll like receptor ligand |
| url | http://europepmc.org/articles/PMC5708771?pdf=render |
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