Business opportunity
Therapy employing T cells modified with chimeric antigen receptors (CARs) is effective in hematological malignancies but not yet in solid tumors. CAR T cell activity in solid tumors is limited by immunosuppressive factors, including transforming growth factor β (TGFβ). Scientists at Oslo University Hosptial, led by Dr. med. Jon Amund Kyte, have developed a switch receptor (SwR), which turns immune suppressive TGFβ-signaling into a stimulatory signal for increased CAR T expansion and functionality. Inven2 is seeking licensees to the patented technology.
Technology description
The SwR is a chimer consisting of the ligand binding domain of TGFβ and the intracellular domain of IL2/15. The Kyte-group has evaluated the SwR in tandem with two variants of a CAR that is developed against STEAP1, a protein highly expressed in prostate cancer and Ewing’s sarcoma, and in sizeable subpopulations of other cancers.
The SwR-STEAP1 CAR variant (JK59) is functionally superior to the parent STEAP1 CAR (JK11) in TGFβ-rich environments in vitro and preliminary in vivo data demonstrate potent anti-tumor effect of the SwR-STEAP1 CAR variant in an animal model of prostate cancer (Fig 1). The data also indicate that the SwR CAR T cells expand and survive in TGFβ-rich environments upon repeated antigen exposure without becoming exhausted and retain potent functionality.
Fig. 1: In vivo data demonstrates POC in a mouse model of prostate cancer over-expressing TGFβ. JK11 is stand-alone STEAP1 CAR, JK59 represents STEAP1 CAR fused with SwR. Graphs represent tumor growth by caliper measurement once a week. Data represent the mean values ± SEM of each group of mice
Advantages
SwR is a platform technology that can be utilized in combination with any cell-based therapy modality (CAR, TCR, NK) impacted by the negative consequences of TGFβ signaling and for other biological targets and cancer types.
IPR
A patent application has been filed.
