Anti-podoplanin antibody against MPM
| Autor: | Toshihiro Izumi, Licht Miyamoto, Kenji Otsuka, Makoto Tobiume, Yasuhiko Nishioka, Chiemi Sato, Kazuyoshi Kawazoe, Yuki Tsuchihashi, Koichiro Tsuchiya, Naoto Okada, Shinji Abe, Yukinari Kato, Satoshi Ogasawara, Mika K. Kaneko |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytotoxicity Immunologic Male Mesothelioma Cancer Research Pathology Lung Neoplasms medicine.medical_treatment Mice 0302 clinical medicine Basic and Clinical Immunology orthotopic xenograft model Cytotoxicity PDPN Antibody-dependent cell-mediated cytotoxicity Membrane Glycoproteins biology NZ‐12 Antibodies Monoclonal General Medicine Pemetrexed Oncology 030220 oncology & carcinogenesis Original Article Drug Therapy Combination Immunotherapy Antibody NZ-12 medicine.drug antibody-dependent cellular cytotoxicity medicine.medical_specialty medicine.drug_class Pleural Neoplasms Antineoplastic Agents Monoclonal antibody 03 medical and health sciences Cell Line Tumor medicine Animals Humans business.industry Mesothelioma Malignant Antibody-Dependent Cell Cytotoxicity Original Articles Complement System Proteins Xenograft Model Antitumor Assays Rats podoplanin Disease Models Animal 030104 developmental biology Podoplanin biology.protein Cancer research business antibody‐dependent cellular cytotoxicity |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. |
| Databáze: | OpenAIRE |
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