Development of a TGFβ-IL-2/15 Switch Receptor for Use in Adoptive Cell Therapy.

ABSTRACT: Therapy employing T cells modified with chimeric antigen receptors (CARs) is effective in hematological malignancies but not yet in solid cancers. CAR T cell activity in solid tumors is limited by immunosuppressive factors, including transforming growth factor β (TGFβ). Here, we describe the development of a switch receptor (SwR), in which the extracellular domains of the TGFβ receptor are fused to the intracellular domains from the IL-2/15 receptor. We evaluated the SwR in tandem with two variants of a CAR that we have developed against STEAP1, a protein highly expressed in prostate cancer. The SwR-CAR T cell activity was assessed against a panel of STEAP1^+/- prostate cancer cell lines with or without over-expression of TGFβ, or with added TGFβ, by use of flow cytometry cytokin

SUBMITTER: Beck C 

PROVIDER: S-EPMC9953633 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature