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Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma

Osteosarcoma is the most common primary bone tumor in both humans and dogs. It is a highly metastatic cancer and therapy has not improved significantly since the inclusion of adjuvant chemotherapy into disease treatment strategies. Osteosarcoma is an immunogenic tumor, and thus development of immuno...

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Autores principales: Kisseberth, William C., Lee, Dean A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215197/
https://www.ncbi.nlm.nih.gov/pubmed/34164452
http://dx.doi.org/10.3389/fvets.2021.672361
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author Kisseberth, William C.
Lee, Dean A.
author_facet Kisseberth, William C.
Lee, Dean A.
author_sort Kisseberth, William C.
collection PubMed
description Osteosarcoma is the most common primary bone tumor in both humans and dogs. It is a highly metastatic cancer and therapy has not improved significantly since the inclusion of adjuvant chemotherapy into disease treatment strategies. Osteosarcoma is an immunogenic tumor, and thus development of immunotherapies for its treatment, especially treatment of microscopic pulmonary metastases might improve outcomes. NK cells are lymphocytes of the innate immune system and can recognize a variety of stressed cells, including cancer cells, in the absence of major histocompatibility complex (MHC)-restricted receptor ligand interactions. NK cells have a role in controlling tumor progression and metastasis and are important mediators of different therapeutic interventions. The core hypothesis of adoptive natural killer (NK) cell therapy is there exists a natural defect in innate immunity (a combination of cancer-induced reduction in NK cell numbers and immunosuppressive mechanisms resulting in suppressed function) that can be restored by adoptive transfer of NK cells. Here, we review the rationale for adoptive NK cell immunotherapy, NK cell biology, TGFβ and the immunosuppressive microenvironment in osteosarcoma, manufacturing of ex vivo expanded NK cells for the dog and provide perspective on the present and future clinical applications of adoptive NK cell immunotherapy in spontaneous osteosarcoma and other cancers in the dog.
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spelling pubmed-82151972021-06-22 Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma Kisseberth, William C. Lee, Dean A. Front Vet Sci Veterinary Science Osteosarcoma is the most common primary bone tumor in both humans and dogs. It is a highly metastatic cancer and therapy has not improved significantly since the inclusion of adjuvant chemotherapy into disease treatment strategies. Osteosarcoma is an immunogenic tumor, and thus development of immunotherapies for its treatment, especially treatment of microscopic pulmonary metastases might improve outcomes. NK cells are lymphocytes of the innate immune system and can recognize a variety of stressed cells, including cancer cells, in the absence of major histocompatibility complex (MHC)-restricted receptor ligand interactions. NK cells have a role in controlling tumor progression and metastasis and are important mediators of different therapeutic interventions. The core hypothesis of adoptive natural killer (NK) cell therapy is there exists a natural defect in innate immunity (a combination of cancer-induced reduction in NK cell numbers and immunosuppressive mechanisms resulting in suppressed function) that can be restored by adoptive transfer of NK cells. Here, we review the rationale for adoptive NK cell immunotherapy, NK cell biology, TGFβ and the immunosuppressive microenvironment in osteosarcoma, manufacturing of ex vivo expanded NK cells for the dog and provide perspective on the present and future clinical applications of adoptive NK cell immunotherapy in spontaneous osteosarcoma and other cancers in the dog. Frontiers Media S.A. 2021-06-07 /pmc/articles/PMC8215197/ /pubmed/34164452 http://dx.doi.org/10.3389/fvets.2021.672361 Text en Copyright © 2021 Kisseberth and Lee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Kisseberth, William C.
Lee, Dean A.
Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma
title Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma
title_full Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma
title_fullStr Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma
title_full_unstemmed Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma
title_short Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma
title_sort adoptive natural killer cell immunotherapy for canine osteosarcoma
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215197/
https://www.ncbi.nlm.nih.gov/pubmed/34164452
http://dx.doi.org/10.3389/fvets.2021.672361
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