Self Destruct Switch

Hematopoietic stem cell transplantation (HSCT) is curative for many leukemia and lymphoma patients. However, HSCT carries a high risk of serious and potentially fatal side effects, which either limits the dose that can be given, resulting in poor efficacy, or prevents the therapy from being used except in the very sickest patients.

Beyond HSCT, adult stem cells hold the promise of cures for a wide range of diseases. In many cases, the stem cells persist after they have served their therapeutic function, with potentially serious but as yet untested long term risks to the patient. The availability of an effective suicide gene is considered by many to be a key to the development of the stem cell therapy field.

CaspaCIDe™ contains the CID Signaling Domain for Caspase 9, an initiator caspase which triggers apoptosis (programmed cell death) when activated, leading to rapid elimination of cells expressing the CaspaCIDe™ protein. CaspaCIDe™ acts as a remote self destruct switch for transplant therapies. Transplant cells are transduced with a CaspCIDe™ gene after they are harvested from the donor (or stem cell line), before they are infused into the patient. Then, if any of the transplanted cells become harmful, or after the cells have served their intended therapeutic purpose, the physician can eliminate them rapidly and effectively by administering AP1903, the CID Master Key. Not only can serious side effects be reversed and chronic treatment to mitigate these side effects be avoided, but treatment related mortality risk could be reduced. This means that more aggressive treatment regimens could be used, and the improved risk profile compared to less effective but otherwise safer treatments means that more patients may become eligible.

In addition to a single CID Binding Domain and Caspase 9 Signaling Domain, the CaspaCIDe™ protein includes a ΔCD19 marker used to sort and isolate cells that have had CaspaCIDe™ successfully inserted, and to detect and monitor these cells after administration.

The first product based on this application of CID technology, CaspaCIDe DLI, addresses the need for a safe way to administer an effective dose of donor T cells following HSCT.