File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1158/1078-0432.CCR-17-0075
- Scopus: eid_2-s2.0-85032198014
- PMID: 28659311
- WOS: WOS:000412160500019
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Memory T cells expressing an NKG2D-CAR efficiently target osteosarcoma cells
Title | Memory T cells expressing an NKG2D-CAR efficiently target osteosarcoma cells |
---|---|
Authors | |
Issue Date | 2017 |
Citation | Clinical Cancer Research, 2017, v. 23, n. 19, p. 5824-5835 How to Cite? |
Abstract | © 2017 American Association for Cancer Research. Purpose: NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor micro-environments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK-cell elimination of osteosarcoma tumor-initiating cells. In this report, we used NKG2D–NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR). Experimental Design: CD45RA- cells from healthy donors were transduced with NKG2D CARs containing 4-1BB and CD3z signaling domains. NKG2D CAR expression was analyzed by flow cytometry. In vitro cytotoxicity of NKG2D-CAR+ CD45RA-T cells against osteosarcoma was evaluated by performing conventional 4-hour europium-TDA release assays. For the in vivo orthotopic model, 531MII YFP-luc osteosarcoma cells were used as targets in NOD-scid IL2Rgnull mice. Results: Lentiviral transduction of NKG2D-4-1BB-CD3z markedly increased NKG2D surface expression in CD45RA- cells. Genetic stability was preserved in transduced cells. In vitro, NKG2D-CAR+ memory T cells showed significantly increased cytolytic activity than untransduced cells against osteosarcoma cell lines, while preserving the integrity of healthy cells. NKG2D-CAR+ memory T cells had considerable antitumor activity in a mouse model of osteosarcoma, whereas untransduced T cells were ineffective. Conclusions: Our results demonstrate NKG2D-4-1BB-CD3z CAR–redirected memory T cells target NKG2DL-expressing osteosarcoma cells in vivo and in vitro and could be a promising immunotherapeutic approach for patients with osteosarcoma. |
Persistent Identifier | http://hdl.handle.net/10722/294518 |
ISSN | 2023 Impact Factor: 10.0 2023 SCImago Journal Rankings: 4.623 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Fernández, Lucía | - |
dc.contributor.author | Metais, Jean Yves | - |
dc.contributor.author | Escudero, Adela | - |
dc.contributor.author | Vela, María | - |
dc.contributor.author | Valentín, Jaime | - |
dc.contributor.author | Vallcorba, Isabel | - |
dc.contributor.author | Leivas, Alejandra | - |
dc.contributor.author | Torres, Juan | - |
dc.contributor.author | Valeri, Antonio | - |
dc.contributor.author | Patiño-García, Ana | - |
dc.contributor.author | Martínez, Joaquín | - |
dc.contributor.author | Leung, Wing | - |
dc.contributor.author | Perez-Martínez, Antonio | - |
dc.date.accessioned | 2020-12-03T08:22:55Z | - |
dc.date.available | 2020-12-03T08:22:55Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Clinical Cancer Research, 2017, v. 23, n. 19, p. 5824-5835 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | http://hdl.handle.net/10722/294518 | - |
dc.description.abstract | © 2017 American Association for Cancer Research. Purpose: NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor micro-environments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK-cell elimination of osteosarcoma tumor-initiating cells. In this report, we used NKG2D–NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR). Experimental Design: CD45RA- cells from healthy donors were transduced with NKG2D CARs containing 4-1BB and CD3z signaling domains. NKG2D CAR expression was analyzed by flow cytometry. In vitro cytotoxicity of NKG2D-CAR+ CD45RA-T cells against osteosarcoma was evaluated by performing conventional 4-hour europium-TDA release assays. For the in vivo orthotopic model, 531MII YFP-luc osteosarcoma cells were used as targets in NOD-scid IL2Rgnull mice. Results: Lentiviral transduction of NKG2D-4-1BB-CD3z markedly increased NKG2D surface expression in CD45RA- cells. Genetic stability was preserved in transduced cells. In vitro, NKG2D-CAR+ memory T cells showed significantly increased cytolytic activity than untransduced cells against osteosarcoma cell lines, while preserving the integrity of healthy cells. NKG2D-CAR+ memory T cells had considerable antitumor activity in a mouse model of osteosarcoma, whereas untransduced T cells were ineffective. Conclusions: Our results demonstrate NKG2D-4-1BB-CD3z CAR–redirected memory T cells target NKG2DL-expressing osteosarcoma cells in vivo and in vitro and could be a promising immunotherapeutic approach for patients with osteosarcoma. | - |
dc.language | eng | - |
dc.relation.ispartof | Clinical Cancer Research | - |
dc.title | Memory T cells expressing an NKG2D-CAR efficiently target osteosarcoma cells | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-17-0075 | - |
dc.identifier.pmid | 28659311 | - |
dc.identifier.scopus | eid_2-s2.0-85032198014 | - |
dc.identifier.volume | 23 | - |
dc.identifier.issue | 19 | - |
dc.identifier.spage | 5824 | - |
dc.identifier.epage | 5835 | - |
dc.identifier.eissn | 1557-3265 | - |
dc.identifier.isi | WOS:000412160500019 | - |
dc.identifier.issnl | 1078-0432 | - |