Regulation of inflammatory cell death by modulation of immune responses in bone marrow transplantation

Bone marrow transplants are used to treat conditions in which the bone marrow is damaged and is not able to produce healthy blood cells like, primary immune deficiencies, as well as leukemia, lymphoma, myeloma, severe aplastic anemia, and more.

Bone marrow transplants are complicated procedures with significant risks like GvHD. Before transplant, the recipient`s bone marrow is destroyed by chemotherapy or radiation in order to prevent rejection. Often, the donor is a family member with human leukocyte antigen (HLA) matching on semi compatible level. It is highly improbable to find a donor with a similar tissue type and as a result the chances of rejection and/or complications increase.

Our project’s aim is to establish a method to attenuate the host`s immune response, thus increasing the chances of a successful transplant.

We hypothesize that inhibition of the innate immune system may reduce the chances of rejection. A pro-inflammatory response after transplantation may activate the enzyme CASPASE-1.

We are working with three strains of mice to demonstrate semi-compatible, syngeneic and fully incompatible transplantations.

Our goal is to treat the donor’s cells with a CASPASE-1 inhibitor prior to transplantation. We hypothesize that inhibition of CASPASE-1 may decrease the chance of transplant rejection by diminishing the host’s immune response.

Currently, in-vitro assays demonstrate a detectable efficacy in lowering innate immune system response by treating donor cells. In-vivo experiments are ongoing and show an increased percentage of transplanted cells. The results may alleviate some of the strictness in HLA matching in the future.