Ontology highlight
ABSTRACT:
PROVIDER: PRJEB16971 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| FOFO01.dat.gz | Other | |||
| FOFO01.fasta.gz | Fasta.gz | |||
| FOFO01.master.dat | Other | |||
| FOFO01.dat.gz | Other |
Items per page: 5 1 - 4 of 4 |
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2012-02-01 | E-GEOD-29993 | biostudies-arrayexpress
Project description:Abstract. The use of large animal spontaneous models of solid cancers, such as dogs with osteosarcoma (OS), can help develop new cancer immunotherapy approaches, including chimeric antigen receptor (CAR) T cells. Therefore, the goal of the present study was to generate canine CAR T cells targeting the B7-H3 (CD276) co-stimulatory molecule overexpressed by several solid cancers, including OS and glioma in both humans and dogs, and to assess their ability to recognize B7-H3 expressed by canine OS cell lines or by canine tumors in xenograft models. A second objective was to determine whether a novel dual CAR that expressed a chemokine receptor together with the B7-H3 CAR improved the activity of the canine CAR T cells. Therefore, in the studies reported here we examined B7-H3 expression by canine OS tumors, evaluated target engagement by canine B7-H3 CAR T cells in vitro, and compared the relative effectiveness of B7-H3 CAR T cells versus B7-H3-CXCR2 dual CAR T cells in canine xenograft models. We found that most canine OS tumors expressed high levels of B7-H3, whereas levels were undetectable on normal dog tissues. In vitro, both B7-H3 CAR T cells demonstrated activation and OS-specific target killing in vitro, but there was significantly greater cytokine production by B7-H3-CXCR2 CAR T cells. In canine OS xenograft models, little antitumor activity was generated by B7-H3 CAR T cells, whereas B7-H3-CXCR2 CAR T cells significantly inhibited tumor growth, inducing complete tumor elimination in most treated mice. These findings indicated therefore that addition of a chemokine receptor could significantly improve the anti-tumor activity of canine B7-H3 CAR T cells, and that evaluation of this new dual CAR construct in dogs with primary or metastatic OS is warranted since such studies could provide a critical and realistic validation of the chemokine receptor concept.
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Project description:B7-H3 (CD276), part of the B7 superfamily, has been shown to play an immunomodulatory role, however its regulation, receptor, and mechanism of action remain unclear. Protein levels of B7-H3 have been previously shown to relate to prostate cancer outcomes and currently, humanized monoclonal antibodies are being investigated for clinical therapeutic use (enoblituzumab, MGA271, Macrogenics). Here we use genomic expression data to examine the relationship of B7-H3 to prostate cancer clinical characteristics and molecular profile.
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2009-08-01 | E-GEOD-15930 | biostudies-arrayexpress
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