Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

Individuals infected with HIV undergo a severe depletion of their T cell compartment, resulting in a state of immune deficiency. T cells are white blood cells that come from bone marrow progenitor cells and develop within a specialized organ, the thymus. One potential mode of treatment for HIV-infected individuals would require the replacement of infected T cells with uninfected bone marrow progenitor cells extracted from donors or cord blood progenitor cells from newborns. However, this approach would rely on acquiring and storing rare and limiting cells from bone marrow donors, with the likely possibility that the donor-derived T cells would ultimately become infected as well. To address this, we are proposing to develop a novel system for the generation of T cell progenitors from defined sources of stem cells. We have demonstrated the feasibility of our in vitro culture system to support and generate large numbers of T cells derived from human cord blood stem cells. These progenitor T cells can be grown in large numbers in tissue culture, genetically modified with ease, and have the potential to develop into any T cell type. In particular, we propose to genetically modify progenitor T cells to give rise to T cells that are resistant to HIV infection. This proposal is highly relevant to the stated aims of the CIHR/III as it provides the foundation for a novel therapeutic approach to generate large numbers of T cells tailored to replace an HIV-infected individual's white blood cells with white blood cells that are resistant to HIV infection.