 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 03, 2024 |
| Title |
Targeting Osteosarcoma with Canine B7-H3 CAR T Cells and Impact of CXCR2 Co-Expression on Functional Activity |
| Organism |
Canis lupus familiaris |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
|
| |
|
| Overall design |
IN the current study we expanded the scope of the original canine B7-H3 CAR T cell studies to evaluate expression of B7-H3 using a larger panel of canine OS tumor cell lines and biopsy tissues. In addition, these studies conducted in vitro and in vivo characterization of a dual B7-H3 CAR construct co-expressing CXCR2.
|
| |
|
| Contributor(s) |
Cao JW, Lake J, Impastato R, Chow L, Perez L, Chubb L, Kurihara J, Verneris MR, Dow S |
| Citation(s) |
38554158 |
| |
| Submission date |
Nov 08, 2023 |
| Last update date |
Apr 03, 2024 |
| Contact name |
Steven Dow |
| E-mail(s) |
sdow@colostate.edu
|
| Organization name |
Colorado State University
|
| Department |
Clinical Sciences
|
| Lab |
ACC 254
|
| Street address |
300 W Drake Rd
|
| City |
Fort Collins |
| State/province |
CO |
| ZIP/Postal code |
80524 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24229 |
Illumina HiSeq 4000 (Canis lupus familiaris) |
|
| Samples (9)
|
|
| Relations |
| BioProject |
PRJNA1037149 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE247355_Car_T-Dual_vs_Single_Normalized_counts_CPM.txt.gz |
467.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...