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Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung
BACKGROUND: Metastases are the leading cause of mortality in many cancer types and lungs are one of the most common sites of metastasis alongside the liver, brain, and bones. In melanoma, 85% of late-stage patients harbor lung metastases. A local administration could enhance the targeting of metasta...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193056/ https://www.ncbi.nlm.nih.gov/pubmed/37192784 http://dx.doi.org/10.1136/jitc-2023-006683 |
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author | Battistoni, Arthur Lantier, Louis di Tommaso, Anne Ducournau, Céline Lajoie, Laurie Samimi, Mahtab Coënon, Loïs Rivière, Clément Epardaud, Mathieu Hertereau, Leslie Poupée-Beaugé, Agathe Rieu, Juliette Mévélec, Marie-Noëlle Lee, Gordon Scott Moiré, Nathalie Germon, Stephanie Dimier-Poisson, Isabelle |
author_facet | Battistoni, Arthur Lantier, Louis di Tommaso, Anne Ducournau, Céline Lajoie, Laurie Samimi, Mahtab Coënon, Loïs Rivière, Clément Epardaud, Mathieu Hertereau, Leslie Poupée-Beaugé, Agathe Rieu, Juliette Mévélec, Marie-Noëlle Lee, Gordon Scott Moiré, Nathalie Germon, Stephanie Dimier-Poisson, Isabelle |
author_sort | Battistoni, Arthur |
collection | PubMed |
description | BACKGROUND: Metastases are the leading cause of mortality in many cancer types and lungs are one of the most common sites of metastasis alongside the liver, brain, and bones. In melanoma, 85% of late-stage patients harbor lung metastases. A local administration could enhance the targeting of metastases while limiting the systemic cytotoxicity. Therefore, intranasal administration of immunotherapeutic agents seems to be a promising approach to preferentially target lung metastases and decrease their burden on cancer mortality. From observations that certain microorganisms induce an acute infection of the tumor microenvironment leading to a local reactivating immune response, microbial-mediated immunotherapy is a next-generation field of investigation in which immunotherapies are engineered to overcome immune surveillance and escape from microenvironmental cancer defenses. METHODS: The goal of our study is to evaluate the potential of the intranasal administration of Neospora caninum in a syngeneic C57BL6 mouse model of B16F10 melanoma lung metastases. It also compares the antitumoral properties of a wild-type N. caninum versus N. caninum secreting human interleukin (IL)-15 fused to the sushi domain of the IL-15 receptor α chain, a potent activator of cellular immune responses. RESULTS: The treatment of murine lung metastases by intranasal administration of an N. caninum engineered to secrete human IL-15 impairs lung metastases from further progression with only 0,08% of lung surface harboring metastases versus 4,4% in wild-type N. caninum treated mice and 36% in untreated mice. The control of tumor development is associated with a strong increase in numbers, within the lung, of natural killer cells, CD8(+) T cells and macrophages, up to twofold, fivefold and sixfold, respectively. Analysis of expression levels of CD86 and CD206 on macrophages surface revealed a polarization of these macrophages towards an antitumoral M1 phenotype. CONCLUSION: Administration of IL-15/IL-15Rα-secreting N. caninum through intranasal administration, a non-invasive route, lend further support to N. caninum-demonstrated clear potential as an effective and safe immunotherapeutic approach for the treatment of metastatic solid cancers, whose existing therapeutic options are scarce. Combination of this armed protozoa with an intranasal route could reinforce the existing therapeutic arsenal against cancer and narrow the spectrum of incurable cancers. |
format | Online Article Text |
id | pubmed-10193056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-101930562023-05-19 Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung Battistoni, Arthur Lantier, Louis di Tommaso, Anne Ducournau, Céline Lajoie, Laurie Samimi, Mahtab Coënon, Loïs Rivière, Clément Epardaud, Mathieu Hertereau, Leslie Poupée-Beaugé, Agathe Rieu, Juliette Mévélec, Marie-Noëlle Lee, Gordon Scott Moiré, Nathalie Germon, Stephanie Dimier-Poisson, Isabelle J Immunother Cancer Oncolytic and Local Immunotherapy BACKGROUND: Metastases are the leading cause of mortality in many cancer types and lungs are one of the most common sites of metastasis alongside the liver, brain, and bones. In melanoma, 85% of late-stage patients harbor lung metastases. A local administration could enhance the targeting of metastases while limiting the systemic cytotoxicity. Therefore, intranasal administration of immunotherapeutic agents seems to be a promising approach to preferentially target lung metastases and decrease their burden on cancer mortality. From observations that certain microorganisms induce an acute infection of the tumor microenvironment leading to a local reactivating immune response, microbial-mediated immunotherapy is a next-generation field of investigation in which immunotherapies are engineered to overcome immune surveillance and escape from microenvironmental cancer defenses. METHODS: The goal of our study is to evaluate the potential of the intranasal administration of Neospora caninum in a syngeneic C57BL6 mouse model of B16F10 melanoma lung metastases. It also compares the antitumoral properties of a wild-type N. caninum versus N. caninum secreting human interleukin (IL)-15 fused to the sushi domain of the IL-15 receptor α chain, a potent activator of cellular immune responses. RESULTS: The treatment of murine lung metastases by intranasal administration of an N. caninum engineered to secrete human IL-15 impairs lung metastases from further progression with only 0,08% of lung surface harboring metastases versus 4,4% in wild-type N. caninum treated mice and 36% in untreated mice. The control of tumor development is associated with a strong increase in numbers, within the lung, of natural killer cells, CD8(+) T cells and macrophages, up to twofold, fivefold and sixfold, respectively. Analysis of expression levels of CD86 and CD206 on macrophages surface revealed a polarization of these macrophages towards an antitumoral M1 phenotype. CONCLUSION: Administration of IL-15/IL-15Rα-secreting N. caninum through intranasal administration, a non-invasive route, lend further support to N. caninum-demonstrated clear potential as an effective and safe immunotherapeutic approach for the treatment of metastatic solid cancers, whose existing therapeutic options are scarce. Combination of this armed protozoa with an intranasal route could reinforce the existing therapeutic arsenal against cancer and narrow the spectrum of incurable cancers. BMJ Publishing Group 2023-05-16 /pmc/articles/PMC10193056/ /pubmed/37192784 http://dx.doi.org/10.1136/jitc-2023-006683 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Oncolytic and Local Immunotherapy Battistoni, Arthur Lantier, Louis di Tommaso, Anne Ducournau, Céline Lajoie, Laurie Samimi, Mahtab Coënon, Loïs Rivière, Clément Epardaud, Mathieu Hertereau, Leslie Poupée-Beaugé, Agathe Rieu, Juliette Mévélec, Marie-Noëlle Lee, Gordon Scott Moiré, Nathalie Germon, Stephanie Dimier-Poisson, Isabelle Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung |
title | Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung |
title_full | Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung |
title_fullStr | Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung |
title_full_unstemmed | Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung |
title_short | Nasal administration of recombinant Neospora caninum secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung |
title_sort | nasal administration of recombinant neospora caninum secreting il-15/il-15rα inhibits metastatic melanoma development in lung |
topic | Oncolytic and Local Immunotherapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193056/ https://www.ncbi.nlm.nih.gov/pubmed/37192784 http://dx.doi.org/10.1136/jitc-2023-006683 |
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