Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody Article Swipe
Yuki Niwa
,
Keito Adachi
,
Kimiyo Tabata
,
Ryoga Ishida
,
Koichiro Hotta
,
Tomomi Ishida
,
Yuji Mano
,
Yoichi Ozawa
,
Yukinori Minoshima
,
Yasuhiro Funahashi
,
Taro Semba
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1535-7163.mct-22-0475
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1535-7163.mct-22-0475
Eribulin is a microtubule dynamics inhibitor with tumor microenvironment modulation activity such as vascular remodeling activity. Here, we investigated antitumor and immunomodulatory activities of eribulin and its liposomal formulation (eribulin-LF) as monotherapies or in combination with anti–programmed death 1 (PD-1) Ab. The antitumor activity of eribulin or eribulin-LF as monotherapy or in combination with anti–PD-1 Ab was examined in a P-glycoprotein–knockout 4T1 model. Eribulin and eribulin-LF showed stronger antitumor activity in immunocompetent mice compared with immunodeficient mice, indicating that they have immunomodulatory activity that underlies its antitumor activity. Combination therapy of eribulin and eribulin-LF with anti–PD-1 Ab showed antitumor activity, and the combination activity of eribulin-LF with anti–PD-1 Ab was observed at a lower dose and longer interval of administration compared with that using eribulin. To examine the immunomodulatory activity of eribulin and eribulin-LF and its underlying mechanisms, we performed flow cytometry, IHC, and gene expression profiling. IHC and flow cytometry revealed that eribulin-LF increased microvessel density and intratumoral populations of cytotoxic T cells and natural killer cells rather than eribulin. Gene expression profiling demonstrated that eribulin-LF induces IFNγ signaling. Furthermore, IHC also showed that eribulin-LF increased infiltration of CD8-positive cells together with increased CD31-positive cells. Eribulin-LF also increased ICAM-1 expression, which is essential for lymphocyte adhesion to vascular endothelial cells. In conclusion, eribulin showed combination antitumor activity with anti–PD-1 Ab via immunomodulation due to its vascular remodeling activity, and the liposomal formulation showed improved antitumor activity over the standard formulation.
Related Topics
Concepts
Eribulin
Flow cytometry
Pharmacology
Cancer research
Medicine
Metastatic breast cancer
Immunology
Breast cancer
Internal medicine
Cancer
Metadata
- Type
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- Language
- en
- Landing Page
- https://doi.org/10.1158/1535-7163.mct-22-0475
- https://aacrjournals.org/mct/article-pdf/22/4/499/3318355/499.pdf
- OA Status
- bronze
- Cited By
- 11
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4318021602
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4318021602Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/1535-7163.mct-22-0475Digital Object Identifier
- Title
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Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 AntibodyWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-01-24Full publication date if available
- Authors
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Yuki Niwa, Keito Adachi, Kimiyo Tabata, Ryoga Ishida, Koichiro Hotta, Tomomi Ishida, Yuji Mano, Yoichi Ozawa, Yukinori Minoshima, Yasuhiro Funahashi, Taro SembaList of authors in order
- Landing page
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https://doi.org/10.1158/1535-7163.mct-22-0475Publisher landing page
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https://aacrjournals.org/mct/article-pdf/22/4/499/3318355/499.pdfDirect link to full text PDF
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YesWhether a free full text is available
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bronzeOpen access status per OpenAlex
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https://aacrjournals.org/mct/article-pdf/22/4/499/3318355/499.pdfDirect OA link when available
- Concepts
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Eribulin, Flow cytometry, Pharmacology, Cancer research, Medicine, Metastatic breast cancer, Immunology, Breast cancer, Internal medicine, CancerTop concepts (fields/topics) attached by OpenAlex
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11Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 6, 2023: 3Per-year citation counts (last 5 years)
- References (count)
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60Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| best_oa_location.raw_source_name | Molecular Cancer Therapeutics |
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| primary_location.id | doi:10.1158/1535-7163.mct-22-0475 |
| primary_location.is_oa | True |
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| primary_location.source.issn | 1535-7163, 1538-8514 |
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| primary_location.source.display_name | Molecular Cancer Therapeutics |
| primary_location.source.host_organization | https://openalex.org/P4310320273 |
| primary_location.source.host_organization_name | American Association for Cancer Research |
| primary_location.source.host_organization_lineage | https://openalex.org/P4310320273 |
| primary_location.license | |
| primary_location.pdf_url | https://aacrjournals.org/mct/article-pdf/22/4/499/3318355/499.pdf |
| primary_location.version | publishedVersion |
| primary_location.raw_type | journal-article |
| primary_location.license_id | |
| primary_location.is_accepted | True |
| primary_location.is_published | True |
| primary_location.raw_source_name | Molecular Cancer Therapeutics |
| primary_location.landing_page_url | https://doi.org/10.1158/1535-7163.mct-22-0475 |
| publication_date | 2023-01-24 |
| publication_year | 2023 |
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