Current SPORE projects are described below. The grant also funds four Career Enhancement Projects and five Development Research Projects. Five previous CEPs and four previous DRPs have been funded since the SPORE grant was awarded to DF/HCC. Annual requests for proposals are issued for additional CEP & DRPs, usually in the spring.
Targeting MLL/Menin in AML
- Aim 1: To assess MLL1/Menin inhibitors in murine models of AML including those with MLL-rearrangements and NPM1 mutations.
- Aim 2: To identify mechanisms of resistance to MLL1/Menin inhibitors and potential combination approaches.
- Aim 3: To perform a phase 1 clinical trial with biomarker assessment of MLL1/Menin inhibitors in relapsed/refractory AML.
Targeting SYK Kinase in AML
- Aim 1: Test the hypothesis that SYK activation engenders resistance to chemotherapy.
- Aim 2: Develop new drug combination strategies with SYK inhibitors in AML through the identification of resistance mechanisms.
- Aim 3: Perform biomarker studies within the context of clinical trials of SYK inhibitor in patients with AML.
Targeting SF3B1 for the treatment of MDS
- Aim 1: Develop pre-clinical models of Sf3b1 mutant MDS
- Aim 2: Explore mechanisms of SF3B1 inhibitor sensitivity and resistance.
- Aim 3: Phase I/II trial of an SF3B1 modulator in MDS and related myeloid neoplasms.
DC AML Fusion Cell Vaccination with Immune checkpoint Blockade
- Aim 1: To conduct a clinical trial in which AML patients with high risk features who undergo allogeneic transplantation in remission will undergo post-transplant vaccination with donor DC/AML fusions alone or in conjunction with HMA.
- Aim 2: To assess the immunologic response following post-transplant vaccination alone or with HMA.
- Aim 3: In a preclinical murine leukemia model, to assess the capacity of the second generation checkpoint inhibitors, RGMb and TIM3 alone and in combination with PD-1 blockade to augment response to DC/AML fusion vaccine.