A5040397625- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Retinoids in leukemia and cellular processes
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Virus-based gene therapy research
- CAR-T cell therapy research
- Cancer Research and Treatments
Sidney Kimmel Comprehensive Cancer Center
2016-2019
Johns Hopkins University
2013-2019
Bloomberg (United States)
2018-2019
Sidney Kimmel Cancer Center
2019
University of Baltimore
2018
Nationwide Children's Hospital
2018
Johns Hopkins Medicine
2013-2017
Johns Hopkins Hospital
2016
Immune-checkpoint inhibition (ICI) has revolutionized treatment in cancers that are naturally immunogenic by enabling infiltration of T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. Tumors possessing complex immunosuppressive TMEs such as breast pancreatic present unique therapeutic obstacles response rates to ICI remain low. Such tumors often recruit myeloid-derived suppressor (MDSCs), whose functioning prohibits both T-cell activation infiltration....
In cancers with tumor-infiltrating lymphocytes (TILs), monoclonal antibodies (mAbs) that block immune checkpoints such as CTLA-4 and PD-1/PD-L1 promote antitumor T-cell immunity. Unfortunately, most fail to respond single-agent immunotherapies. T regulatory cells, myeloid derived suppressor cells (MDSCs), extensive stromal networks within the tumor microenvironment (TME) dampen responses by preventing infiltration and/or activation. Few studies have explored combinations of immune-checkpoint...
Abstract FMS-like tyrosine kinase-3 (FLT3) kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia (AML). We hypothesized that FLT3/internal tandem duplication (ITD) cells exhibit mechanisms of intrinsic signaling adaptation TKI treatment are associated with an incomplete response. Here, we identified reactivation ERK within hours following FLT3/ITD AML selective FLT3. When these were treated both FLT3 and MEK combination, was abrogated anti-leukemia...
Significance FMS-like tyrosine kinase 3 (FLT3) is mutated in approximately a third of acute myeloid leukemia cases, predominantly the forms FLT3/internal tandem duplication mutations juxtamembrane domain or point domain. Although both activate FLT3, they confer distinctive prognosis. To elucidate mechanisms behind this prognostic difference, we have generated knock-in mouse model with FLT3/D835Y mutation that converts aspartic acid to tyrosine. Further comparisons mice previously generated,...
There have been a number of clinical trials testing the efficacy FMS-like tyrosine kinase-3 (FLT3) kinase inhibitors (TKI) in patients with acute myeloid leukemia (AML) harboring constitutively activating mutation FLT3. However, there has limited efficacy, most often because inadequate achievement FLT3 inhibition through variety mechanisms. In previous study, TTT-3002 was identified as novel inhibitor potent activity to date against internal tandem duplication (FLT3/ITD) mutations. Here, is...
Abstract A hallmark of many non-immunogenic cancers is the lack tumor infiltrating lymphocytes (TIL) and/or failure to mount a robust anti-tumor T cell response via multiple mechanisms. The presence regulatory cells and myeloid derived suppressor (MDSCs) serve dampen immune response, furthermore, antigen-specific tolerance limits efficacy therapeutic cancer vaccines. CD40 signaling critical decision whether cytotoxic become primed or tolerized. Administration monoclonal agonistic antibody...
Abstract Immune tolerance by multiple mechanisms is a major obstacle in the implementation of successful immunotherapy. T regulatory cells (Tregs) and myeloid derived suppressor (MDSCs) suppress immune response, presence extensive stromal networks within tumor microenvironment (TME) can prevent cell infiltration many types. Furthermore, antigen-specific limits efficacy therapeutic cancer vaccines. CD40 expressed on antigen presenting cells, signaling critical to decision whether cytotoxic...
Abstract Oncolytic viruses are an emerging class of cancer therapeutics that couple cytotoxicity with the induction antitumor immune response. Host-virus interactions complex and modulated by a tumor microenvironment whose immunosuppressive activities can limit effectiveness immunotherapies. In effort to improve this aspect oncolytic virotherapy, we combined herpes virus HSV1716 TGFβR1 inhibitor A8301 treat syngeneic models murine rhabdomyosarcoma. Mice received or alone showed little no...
<div>Abstract<p>There have been a number of clinical trials testing the efficacy FMS-like tyrosine kinase-3 (FLT3) kinase inhibitors (TKI) in patients with acute myeloid leukemia (AML) harboring constitutively activating mutation FLT3. However, there has limited efficacy, most often because inadequate achievement FLT3 inhibition through variety mechanisms. In previous study, TTT-3002 was identified as novel inhibitor potent activity to date against internal tandem duplication...