Chimeric Antigen Receptor-modified T cells targeting EphA2 for the immunotherapy of paediatric bone tumours.

Abstract

Chimeric Antigen Receptor (CAR) T-cell therapy, as an approved treatment option for patients with B cell malignancies, demonstrates that genetic modification of autologous immune cells is an effective anti-cancer regimen. Erythropoietin-producing Hepatocellular receptor tyrosine kinase class A2 (EphA2) is a tumour associated antigen expressed on a range of sarcomas, including paediatric osteosarcoma (OS) and Ewing sarcoma (ES). We tested human EphA2 directed CAR T cells for their capacity to target and kill human OS and ES tumour cells using in vitro and in vivo assays, demonstrating that EphA2 CAR T cells have potent anti-tumour efficacy in vitro and can eliminate established OS and ES tumours in vivo in a dose and delivery route dependent manner. Next, in an aggressive metastatic OS model we demonstrated that systemically infused EphA2 CAR T cells can traffic to and eradicate tumour deposits in murine livers and lungs. These results support further pre-clinical evaluation of EphA2 CAR T cells to inform the design of early phase clinical trial protocols to test the feasibility and safety of this immune cell therapy in paediatric bone sarcoma patients.

• Authors: Kenneth Hsu, Shiloh Middlemiss, Federica Saletta, Stephen Gottschalk, Geoffrey B McCowage, Belinda Kramer
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 28 Issue 3-4 Pg. 321-334 (04 2021) ISSN: 1476-5500 [Electronic] England
• PMID: 32873870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• EPHA2 protein, human
• Receptor, EphA2

Topics

• Animals
• Bone Neoplasms (genetics, immunology, therapy)
• Female
• Humans
• Immunotherapy, Adoptive (methods)
• Mice
• Mice, Inbred NOD
• Molecular Targeted Therapy
• Receptor, EphA2 (immunology)
• T-Lymphocytes (immunology)