Our shRNA armored CAR, or shARC, platform explores an armoring CAR technology in conjunction with our shRNA platform to develop allogeneic CAR Ts to further optimize cell therapies for cancer patients. Armored CAR Ts are T cells engineered to co-express a CAR as well as secrete specific cytokines in order to increase the anti-tumor activity of CAR T cells. These armored CAR Ts fortify the cell therapy to overcome the hostile tumor microenvironment (TME) and drive a strong anti-tumor effect.
Our first armored CAR Ts are focused on the expression of Interleukin-18 (IL-18). We believe IL-18 is an ideal cytokine for shARC as it directly increases the anti-cancer activity of CAR T cells while also altering the balance of pro- and anti-inflammatory cells within tumor tissue.
Arming CAR Ts with IL-18 offer two key effects:
- an autocrine effect, where the IL-18 cytokine can have a beneficial impact on the CAR T cell function and;
- a paracrine effect, where the IL-18 cytokine can drive the strongly immunosuppressive environment, present within the majority of tumors, to an environment that's more pro-inflammatory.
IL-18 can modulate not just the CAR T but also the local tumor environment, which can drive meaningful clinical benefit.
shARC™ Platform to develop a series of candidates for the treatment of solid tumors and hematological malignancies
We introduced our shARC platform in 2021 and are focusing our efforts on IL-18 for preclinical CAR T candidates. In vivo data show a proposed mechanism for superior proliferation and anti-tumor activity with CAR Ts secreting 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 therapy1. We are curretnly exploring allogeneic NKG2D receptor CAR T candidates in discovery stage that leverage our shARC Platform.
We truly believe armoring CARs alongside our shRNA technology offers a tremendous opportunity to drive a series of differentiated allogeneic CAR T candidates for both solid tumors and hematological malignancies.
1. 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