Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma
Sarcomas are a diverse group of bone and soft tissue tumors that account for over 10% of childhood cancers. Outcomes are particularly poor for children with refractory, relapsed, or metastatic disease. Chimeric antigen receptor T (CAR T) cells are an exciting form of adoptive cell therapy that poten...
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doaj-cfd4fe87add6419db3fee5bc063c4c7f2021-09-25T23:50:32ZengMDPI AGCancers2072-66942021-09-01134704470410.3390/cancers13184704Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric SarcomaRachael L. Terry0Deborah Meyran1Emmy D. G. Fleuren2Chelsea Mayoh3Joe Zhu4Natacha Omer5David S. Ziegler6Michelle Haber7Phillip K. Darcy8Joseph A. Trapani9Paul J. Neeson10Paul G. Ekert11Children’s Cancer Institute, Randwick 2031, AustraliaCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3000, AustraliaChildren’s Cancer Institute, Randwick 2031, AustraliaChildren’s Cancer Institute, Randwick 2031, AustraliaCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3000, AustraliaTranslational Innate Immunotherapy, University of Queensland Diamantina Institute (UQDI), Brisbane 4102, AustraliaChildren’s Cancer Institute, Randwick 2031, AustraliaChildren’s Cancer Institute, Randwick 2031, AustraliaCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3000, AustraliaCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3000, AustraliaCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3000, AustraliaChildren’s Cancer Institute, Randwick 2031, AustraliaSarcomas are a diverse group of bone and soft tissue tumors that account for over 10% of childhood cancers. Outcomes are particularly poor for children with refractory, relapsed, or metastatic disease. Chimeric antigen receptor T (CAR T) cells are an exciting form of adoptive cell therapy that potentially offers new hope for these children. In early trials, promising outcomes have been achieved in some pediatric patients with sarcoma. However, many children do not derive benefit despite significant expression of the targeted tumor antigen. The success of CAR T cell therapy in sarcomas and other solid tumors is limited by the immunosuppressive tumor microenvironment (TME). In this review, we provide an update of the CAR T cell therapies that are currently being tested in pediatric sarcoma clinical trials, including those targeting tumors that express HER2, NY-ESO, GD2, EGFR, GPC3, B7-H3, and MAGE-A4. We also outline promising new CAR T cells that are in pre-clinical development. Finally, we discuss strategies that are being used to overcome tumor-mediated immunosuppression in solid tumors; these strategies have the potential to improve clinical outcomes of CAR T cell therapy for children with sarcoma.https://www.mdpi.com/2072-6694/13/18/4704sarcomaimmunotherapyCAR T cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachael L. Terry Deborah Meyran Emmy D. G. Fleuren Chelsea Mayoh Joe Zhu Natacha Omer David S. Ziegler Michelle Haber Phillip K. Darcy Joseph A. Trapani Paul J. Neeson Paul G. Ekert |
spellingShingle |
Rachael L. Terry Deborah Meyran Emmy D. G. Fleuren Chelsea Mayoh Joe Zhu Natacha Omer David S. Ziegler Michelle Haber Phillip K. Darcy Joseph A. Trapani Paul J. Neeson Paul G. Ekert Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma Cancers sarcoma immunotherapy CAR T cells |
author_facet |
Rachael L. Terry Deborah Meyran Emmy D. G. Fleuren Chelsea Mayoh Joe Zhu Natacha Omer David S. Ziegler Michelle Haber Phillip K. Darcy Joseph A. Trapani Paul J. Neeson Paul G. Ekert |
author_sort |
Rachael L. Terry |
title |
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma |
title_short |
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma |
title_full |
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma |
title_fullStr |
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma |
title_full_unstemmed |
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma |
title_sort |
chimeric antigen receptor t cell therapy and the immunosuppressive tumor microenvironment in pediatric sarcoma |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-09-01 |
description |
Sarcomas are a diverse group of bone and soft tissue tumors that account for over 10% of childhood cancers. Outcomes are particularly poor for children with refractory, relapsed, or metastatic disease. Chimeric antigen receptor T (CAR T) cells are an exciting form of adoptive cell therapy that potentially offers new hope for these children. In early trials, promising outcomes have been achieved in some pediatric patients with sarcoma. However, many children do not derive benefit despite significant expression of the targeted tumor antigen. The success of CAR T cell therapy in sarcomas and other solid tumors is limited by the immunosuppressive tumor microenvironment (TME). In this review, we provide an update of the CAR T cell therapies that are currently being tested in pediatric sarcoma clinical trials, including those targeting tumors that express HER2, NY-ESO, GD2, EGFR, GPC3, B7-H3, and MAGE-A4. We also outline promising new CAR T cells that are in pre-clinical development. Finally, we discuss strategies that are being used to overcome tumor-mediated immunosuppression in solid tumors; these strategies have the potential to improve clinical outcomes of CAR T cell therapy for children with sarcoma. |
topic |
sarcoma immunotherapy CAR T cells |
url |
https://www.mdpi.com/2072-6694/13/18/4704 |
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