CubiCAR cells are designed to be killed by the monoclonal antibody, rituximab, in patients with an overactive immune response.
Many different approaches to the personalized treatment of cancer are under development today. Cell therapies – particularly CAR (chimeric antigen receptor)-T cell therapies – are attracting significant attention. Two types are advancing through clinical trials – autologous therapies, which are developed directly from individual patient cells, and allogenic, which are derived from donor cells, produced in large quantities and available “off-the-shelf.” Autologous therapies pose manufacturing and logistics challenges, while allogenic therapies must overcome difficulties with immune rejection.
All CAR-T therapies face an additional challenge related to their safety. These therapies are designed to harness the body’s immune system to destroy cancer cells. In some patients, the immune response is stronger than expected, and both cancer and healthy cells are attacked.
One approach is to design into the CART-T cells a mechanism for destroying them in the event of an overactive immune response. Several companies, such as Cellectis, Bellicum and Gilead Sciences (which purchased Kite Pharma), are developing such therapies.
Cellectic is going even further. Its CubiCAR CAR-T technology is an all-in-one construct with an embedded multifunctional tag for the purification, tracking and elimination of CAR-T cells. The technology may enable the production of allogenic CAR-T therapies.
The CubiCAR CAR-T cells are destroyed by the monoclonal antibody rituximab in vivo, allowing the treatment of patients with excessive immune responses following cell therapy treatment. CubiCAR is also designed to eliminate the risk of generating cells that lack this safety switch during manufacturing, which can result when certain other functionalities are present on the T cell surfaces.
Allogenic CAR-T therapies are attractive because they could reduce the manufacturing complexity and thus both time and cost. “The transformational impact of autologous CAR T therapy for the treatment of hematologic cancers has been firmly established,” said Barbra Sasu, Ph.D., chief scientific officer of Allogene, which has rights to 17 allogenic Cellectis assets. “We plan to evaluate this CubiCAR approach and other novel CAR T engineering developed in partnership with our colleagues at Cellectis across our extensive CAR T pipeline.”