Cellular therapy has enormous potential for the treatment of a broad range of diseases. Currently, hematopoietic cell transplantation (HCT) serves as the major example of the use of cell based therapeutics currently practiced in clinical medicine. Many advances in the understanding of the role of specific cell populations performed in animal models demonstrate the potential for the extension of this mode of therapy into a number of other important areas. However, key limitations including the availability of suitably matched donors and the risk of graft vs. host disease (GVHD) limit the effectiveness and application of this potential treatment strategy. In this GO TRIP stage I proposal we will attempt to translate novel insights from our laboratory and others that have demonstrated the potential functional role of key cell populations that could have a major impact in the success and application of cellular therapeutics in the clinic. In the proposal we will pursue a clinical trial of CD4+CD25+FoxP3+ regulatory T cells (Treg) in HCT and to attempt to develop at least one other cellular therapeutic with strong preclinical data. Central to the successful application of these treatment strategies is the effective isolation of sometimes rare populations of cells using high speed cell sorting on a clinical scale. The proposal seeks support to implement a clinical trial of Treg where development including scale-up, validation and IND submission has already been completed. The trial will be pursued in patients undergoing haploidentical transplantation due to the unmet clinical need and the view that this clinical setting will allow for rapid assessment of Treg function. Further, the proposal will establish a Translation Team to evaluate three other potential cellular populations including purified hematopoietic stem cells, common lymphoid progenitor cells and effector memory CD8+ T cells which have all been studied by investigators within the Program with the goal of bringing one or possibly two of these proposals forward to development, validation and IND submission. The proposal will advance critical science, develop novel technology and provide critical jobs for the important development and implementation of novel cellular therapeutics.
A Clinical Trials Project Manager will be hired to oversee the operations of a multicenter, Phase III clinical trial. For elderly patients with acute myeloid leukemia, this trial is attempting to determine if allogeneic hematopoietic cell transplantation can improve the poor prognoses typically seen in this patient population. Preliminary studies, so far, have demonstrated favorable results with this specific type of transplant.
| Negrin, Robert S (2011) Role of regulatory T cell populations in controlling graft vs host disease. Best Pract Res Clin Haematol 24:453-7 |
