IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.
Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinas...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4501840?pdf=render |
| _version_ | 1817994736606117888 |
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| author | Xin Huang Haein Park Joseph Greene James Pao Erin Mulvey Sophia X Zhou Catherine M Albert Fred Moy Deepali Sachdev Douglas Yee Christoph Rader Carl V Hamby David M Loeb Mitchell S Cairo Xianzheng Zhou |
| author_facet | Xin Huang Haein Park Joseph Greene James Pao Erin Mulvey Sophia X Zhou Catherine M Albert Fred Moy Deepali Sachdev Douglas Yee Christoph Rader Carl V Hamby David M Loeb Mitchell S Cairo Xianzheng Zhou |
| author_sort | Xin Huang |
| collection | DOAJ |
| description | Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients. |
| first_indexed | 2024-04-14T01:56:13Z |
| format | Article |
| id | doaj.art-4e8779c3a18148f587ae7ab7b4739633 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T01:56:13Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4e8779c3a18148f587ae7ab7b47396332022-12-22T02:19:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013315210.1371/journal.pone.0133152IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.Xin HuangHaein ParkJoseph GreeneJames PaoErin MulveySophia X ZhouCatherine M AlbertFred MoyDeepali SachdevDouglas YeeChristoph RaderCarl V HambyDavid M LoebMitchell S CairoXianzheng ZhouPatients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.http://europepmc.org/articles/PMC4501840?pdf=render |
| spellingShingle | Xin Huang Haein Park Joseph Greene James Pao Erin Mulvey Sophia X Zhou Catherine M Albert Fred Moy Deepali Sachdev Douglas Yee Christoph Rader Carl V Hamby David M Loeb Mitchell S Cairo Xianzheng Zhou IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. PLoS ONE |
| title | IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. |
| title_full | IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. |
| title_fullStr | IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. |
| title_full_unstemmed | IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. |
| title_short | IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. |
| title_sort | igf1r and ror1 specific car t cells as a potential therapy for high risk sarcomas |
| url | http://europepmc.org/articles/PMC4501840?pdf=render |
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