IMMU-23. TARGETING THE CD200 CHECKPOINT TO ENHANCE IMMUNOTHERAPY FOR CNS TUMORS Article Swipe
Christopher L. Moertel
,
G. Elizabeth Pluhar
,
Elisabet Ampudia-Mesias
,
Zhengming Xiong
,
Christopher A. Pennell
,
Susan K. Rathe
,
David A. Largaespada
,
Michael R. Olin
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noz036.142
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noz036.142
Numerous clinical trials targeting immune checkpoints have failed to enhance survival in patients with CNS tumors. We are targeting a unique checkpoint, CD200, which controls the immune system through paired inhibitory and activation receptors. The CD200 checkpoint interferes with tumor-immune interactions through secretion of CD200 from tumors inducing an immunosuppressive environment and up regulation of CD200 in tumor-associated vascular endothelial cells, creating an immunological blood brain barrier. We are targeting the activation receptor with a peptide ligand (CD200AR-L) that activates antigen-presenting cells and enhances dendritic cell maturation, resulting in antigen specific T cell cytokine production. Directing the immune system requires introduction of an antigen such as autologous or allogeneic brain tumor lysate for non-immunogenic tumors such as CNS tumors. Treatment with CD200AR-L significantly extends survival in two murine glioma models. Additionally, an ongoing pilot study treating companion dogs with high-grade glioma using a canine specific CD200 peptide ligand in combination with an autologous tumor lysate vaccine increased median survival to 330 days, compared to 194 days with lysate alone. Currently, 41% of the dogs are alive; the longest living dog is now 810 days post-surgery. 28% of dogs died of non-tumor related deaths. In contrast, 100% of the dogs in the tumor lysate-only group died of tumor recurrence. We have developed human CD200 peptide ligands that enhance cytokine secretion, dendritic cell maturation, and antigen-specific immune response in vitro. In addition, we have shown that a ligand targeting the activation receptor (CD200AR-L) results in down regulation of PD-1. We have also demonstrated that the use of a CD200AR-L resulted in a significant survival benefit in a murine breast carcinoma model. In this light, CD200AR-L may be a powerful immunotherapy platform for other solid tumors. This innovative research may provide a significant breakthrough for the field of cancer immunotherapy.
Related Topics
Concepts
Immune system
Immunotherapy
Antigen
Cancer research
Glioma
Cytokine
Dendritic cell
Immunology
Immune checkpoint
Biology
Medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/neuonc/noz036.142
- https://academic.oup.com/neuro-oncology/article-pdf/21/Supplement_2/ii97/28443194/noz036.142.pdf
- OA Status
- bronze
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2940845724Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/neuonc/noz036.142Digital Object Identifier
- Title
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IMMU-23. TARGETING THE CD200 CHECKPOINT TO ENHANCE IMMUNOTHERAPY FOR CNS TUMORSWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2019Year of publication
- Publication date
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2019-04-01Full publication date if available
- Authors
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Christopher L. Moertel, G. Elizabeth Pluhar, Elisabet Ampudia-Mesias, Zhengming Xiong, Christopher A. Pennell, Susan K. Rathe, David A. Largaespada, Michael R. OlinList of authors in order
- Landing page
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https://doi.org/10.1093/neuonc/noz036.142Publisher landing page
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https://academic.oup.com/neuro-oncology/article-pdf/21/Supplement_2/ii97/28443194/noz036.142.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://academic.oup.com/neuro-oncology/article-pdf/21/Supplement_2/ii97/28443194/noz036.142.pdfDirect OA link when available
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Immune system, Immunotherapy, Antigen, Cancer research, Glioma, Cytokine, Dendritic cell, Immunology, Immune checkpoint, Biology, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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