Oncolytic immunotherapy and bortezomib synergy improves survival of refractory multiple myeloma in a preclinical model
| العنوان: | Oncolytic immunotherapy and bortezomib synergy improves survival of refractory multiple myeloma in a preclinical model |
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| المؤلفون: | Karen A. Kopciuk, Victor H Jimenez-Zepeda, Satbir Thakur, Douglas A. Stewart, Kathy Gratton, Marta Chesi, P. Leif Bergsagel, Gerard J. Nuovo, Zhong Qiao Shi, Chandini M. Thirukkumaran, Ahmed A. Mostafa, Joanne Luider, Matthew C. Coffey, Yuan Dong, Alex Chin, Don Morris, Ailian Yang |
| المصدر: | Blood Advances. 3:797-812 |
| بيانات النشر: | American Society of Hematology, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | medicine.medical_treatment, Virus Replication, Bortezomib, Mice, Immune system, Cell Line, Tumor, medicine, Animals, Humans, Multiple myeloma, Oncolytic Virotherapy, Salvage Therapy, Tumor microenvironment, Lymphoid Neoplasia, business.industry, Endothelial Cells, Immunosuppression, Hematology, Immunotherapy, medicine.disease, Combined Modality Therapy, Xenograft Model Antitumor Assays, Oncolytic virus, Oncolytic Viruses, Cytokine, Cancer research, Multiple Myeloma, business, medicine.drug |
| الوصف: | The oncolytic reovirus (RV) has demonstrated clinical efficacy and minimal toxicity in a variety of cancers, including multiple myeloma (MM). MM is a malignancy of plasma cells that is considered treatable but incurable because of the 90% relapse rate that is primarily from drug resistance. The systemic nature of MM and the antitumor immunosuppression by its tumor microenvironment presents an ongoing therapeutic challenge. In the present study, we demonstrate that RV synergizes with the standard-of-care MM drug bortezomib (BTZ) and, importantly, enhances its therapeutic potential in therapy-resistant human MM cell lines in vitro. Using the syngeneic Vk*MYC BTZ-resistant immunocompetent transplantable MM murine model, we also demonstrate that mice harboring BTZ-insensitive MM tumors respond to the RV/BTZ combination treatment in terms of decreased tumor burden and improved overall survival (P < .00001). We demonstrate that BTZ augments RV replication in tumor-associated endothelial cells and myeloma cells, leading to enhanced viral delivery and thereby stimulating cytokine release, immune activity, apoptosis, and reduction of the MM-associated immune suppression. We conclude that combined RV/BTZ is an attractive therapeutic strategy with no safety signals for the treatment of MM. |
| تدمد: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2018025593 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2287b6246c0236920f16c7e541e9e210 https://doi.org/10.1182/bloodadvances.2018025593 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2287b6246c0236920f16c7e541e9e210 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24739537 24739529 |
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| DOI: | 10.1182/bloodadvances.2018025593 |