Our shRNA armored CAR, or shARC, platform explores an armoring CAR technology in conjunction with our shRNA platform to further optimize CAR T-cell therapies for cancer patients. Armored CAR T-cells are T cells engineered to co-express a CAR and specific cytokines in order to increase their anti-tumor activity. This armoring fortifies the cell therapy to overcome the hostile tumor microenvironment (TME), characterizing most tumors, and drives a strong anti-tumor effect.
Our first armored CAR T-cell candidates are focused on the expression of Interleukin-18 (IL-18). IL-18 is a member of the IL-1 family of cytokines that plays an important role in the T-cell-helper type 1 (Th1) response, by inducing interferon (IFN) gamma production in T-cells and natural killer (NK) cells.
We believe IL-18 is an ideal cytokine for shARC as it could:
- directly increase the anti-cancer activity and function of CAR T-cells via an autocrine effect ;
- alter the balance of pro- and anti-inflammatory cells within tumor tissues via a paracrine effect, where the IL-18 cytokine can drive the strongly immunosuppressive TME to become more pro-inflammatory.
IL-18 can modulate not just the CAR T-cells but also the local tumor microenvironment, which can drive meaningful anti-tumor effect
shARC™ Platform to develop a series of candidates for the treatment of solid tumors and hematological malignancies
We are focusing our efforts on IL-18 for preclinical CAR T-cell candidates. In vivo data show superior anti-tumor activity with CAR T-cells secreting IL-18 compared with those not expressing IL-18. Furthermore, clinical studies using recombinant IL-18 have shown the cytokine to be well tolerated, supporting its safety for use in an armored CAR T therapy .
. Robertson, Michael J et al. “A dose-escalation study of recombinant human interleukin-18 in combination with rituximab in patients with non-Hodgkin lymphoma.” Journal of immunotherapy (Hagerstown, Md. : 1997) vol. 36,6 (2013): 331-41. doi:10.1097/CJI.0b013e31829d7e2e