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Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer

Despite the recent emergence of immune checkpoint inhibitors, clinical outcomes of metastatic NSCLC patients remain poor, pointing out the unmet need to develop novel therapies to enhance the anti-tumor immune response in NSCLC. In this regard, aberrant expression of the immune checkpoint molecule C...

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Autores principales: Flieswasser, Tal, Van den Eynde, Astrid, Freire Boullosa, Laurie, Melis, Jöran, Hermans, Christophe, Merlin, Céline, Lau, Ho Wa, Van Audenaerde, Jonas, Lardon, Filip, Smits, Evelien, Pauwels, Patrick, Jacobs, Julie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10038060/
https://www.ncbi.nlm.nih.gov/pubmed/36970072
http://dx.doi.org/10.1080/2162402X.2023.2192100
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author Flieswasser, Tal
Van den Eynde, Astrid
Freire Boullosa, Laurie
Melis, Jöran
Hermans, Christophe
Merlin, Céline
Lau, Ho Wa
Van Audenaerde, Jonas
Lardon, Filip
Smits, Evelien
Pauwels, Patrick
Jacobs, Julie
author_facet Flieswasser, Tal
Van den Eynde, Astrid
Freire Boullosa, Laurie
Melis, Jöran
Hermans, Christophe
Merlin, Céline
Lau, Ho Wa
Van Audenaerde, Jonas
Lardon, Filip
Smits, Evelien
Pauwels, Patrick
Jacobs, Julie
author_sort Flieswasser, Tal
collection PubMed
description Despite the recent emergence of immune checkpoint inhibitors, clinical outcomes of metastatic NSCLC patients remain poor, pointing out the unmet need to develop novel therapies to enhance the anti-tumor immune response in NSCLC. In this regard, aberrant expression of the immune checkpoint molecule CD70 has been reported on many cancer types, including NSCLC. In this study, the cytotoxic and immune stimulatory potential of an antibody-based anti-CD70 (aCD70) therapy was explored as single agent and in combination with docetaxel and cisplatin in NSCLC in vitro and in vivo. Anti-CD70 therapy resulted in NK-mediated killing of NSCLC cells and increased production of pro-inflammatory cytokines by NK cells in vitro. The combination of chemotherapy and anti-CD70 therapy further enhanced NSCLC cell killing. Moreover, in vivo findings showed that the sequential treatment of chemo-immunotherapy resulted in a significant improved survival and delayed tumor growth compared to single agents in Lewis Lung carcinoma-bearing mice. The immunogenic potential of the chemotherapeutic regimen was further highlighted by increased numbers of dendritic cells in the tumor-draining lymph nodes in these tumor-bearing mice after treatment. The sequential combination therapy resulted in enhanced intratumoral infiltration of both T and NK cells, as well as an increase in the ratio of CD8+ T cells over Tregs. The superior effect of the sequential combination therapy on survival was further confirmed in a NCI-H1975-bearing humanized IL15-NSG-CD34+ mouse model. These novel preclinical data demonstrate the potential of combining chemotherapy and aCD70 therapy to enhance anti-tumor immune responses in NSCLC patients.
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spelling pubmed-100380602023-03-25 Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer Flieswasser, Tal Van den Eynde, Astrid Freire Boullosa, Laurie Melis, Jöran Hermans, Christophe Merlin, Céline Lau, Ho Wa Van Audenaerde, Jonas Lardon, Filip Smits, Evelien Pauwels, Patrick Jacobs, Julie Oncoimmunology Original Research Despite the recent emergence of immune checkpoint inhibitors, clinical outcomes of metastatic NSCLC patients remain poor, pointing out the unmet need to develop novel therapies to enhance the anti-tumor immune response in NSCLC. In this regard, aberrant expression of the immune checkpoint molecule CD70 has been reported on many cancer types, including NSCLC. In this study, the cytotoxic and immune stimulatory potential of an antibody-based anti-CD70 (aCD70) therapy was explored as single agent and in combination with docetaxel and cisplatin in NSCLC in vitro and in vivo. Anti-CD70 therapy resulted in NK-mediated killing of NSCLC cells and increased production of pro-inflammatory cytokines by NK cells in vitro. The combination of chemotherapy and anti-CD70 therapy further enhanced NSCLC cell killing. Moreover, in vivo findings showed that the sequential treatment of chemo-immunotherapy resulted in a significant improved survival and delayed tumor growth compared to single agents in Lewis Lung carcinoma-bearing mice. The immunogenic potential of the chemotherapeutic regimen was further highlighted by increased numbers of dendritic cells in the tumor-draining lymph nodes in these tumor-bearing mice after treatment. The sequential combination therapy resulted in enhanced intratumoral infiltration of both T and NK cells, as well as an increase in the ratio of CD8+ T cells over Tregs. The superior effect of the sequential combination therapy on survival was further confirmed in a NCI-H1975-bearing humanized IL15-NSG-CD34+ mouse model. These novel preclinical data demonstrate the potential of combining chemotherapy and aCD70 therapy to enhance anti-tumor immune responses in NSCLC patients. Taylor & Francis 2023-03-23 /pmc/articles/PMC10038060/ /pubmed/36970072 http://dx.doi.org/10.1080/2162402X.2023.2192100 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Original Research
Flieswasser, Tal
Van den Eynde, Astrid
Freire Boullosa, Laurie
Melis, Jöran
Hermans, Christophe
Merlin, Céline
Lau, Ho Wa
Van Audenaerde, Jonas
Lardon, Filip
Smits, Evelien
Pauwels, Patrick
Jacobs, Julie
Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
title Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
title_full Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
title_fullStr Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
title_full_unstemmed Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
title_short Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
title_sort targeting cd70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10038060/
https://www.ncbi.nlm.nih.gov/pubmed/36970072
http://dx.doi.org/10.1080/2162402X.2023.2192100
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