Our leukemia research team is working to develop better treatments for all types of leukemia in adult patients. Clinical research in leukemia is conducted by a multidisciplinary team that includes hematologists, medical oncologists, radiologists, pathologists, surgeons, and specialists in bone marrow transplantation and infectious diseases.
Our investigators are at the leading edge of developing new treatments for leukemia, including the development of new targeted therapies and immunologic drugs. We also collaborate very closely with basic scientists working in the laboratory, taking important discoveries from bench to bedside.
Among our recent research accomplishments:
- Our researchers are identifying activated signaling molecules in chronic lymphocytic leukemia (CLL), including members of the MAPL, STAT, and NF-kB pathways in freshly isolated CLL cells, distinguished by altered levels of phosphorylation. The goal is to identify key pathways used by CLL and apply this to the evaluation of new therapeutic candidate molecules.
- We have evaluated the usefulness of carbon nanotubes for in vivo imaging by whole-body positron emission tomography scans of radiolabeled nanotubes in mice. The nanotubes accumulated in the kidney, liver, and spleen with rapid blood clearance, suggesting that they could be used to deliver short-lived radionuclides in diagnostic applications. PLoS One. 2007 Sep 19;2(9):e907. [PubMed Abstract]
- Drugs that act by modulating gene transcription, such as DNA methyltransferase (DMT) inhibitors and histone deacetylase (HDAC) inhibitors, remain a major focus in the development of new leukemia therapies.
- We are examining the HDAC inhibitor depsipeptide in patients with myelodysplastic syndrome and acute myelogenous leukemia. A pilot trial revealed cumulative nonhematologic toxicities including fatigue and gastrointestinal symptoms in some patients, with one patient having a complete response. We also found that depsipeptide induced apoptosis in peripheral blood and bone marrow mononuclear cells of most evaluable patients. Clin Cancer Res. 2008 Feb 1;14(3):826-32. [PubMed Abstract]
- Alpha particles are high-energy radiations capable of killing in the range of one to three cells. We are developing new therapeutic approaches in which alpha particles are targeted to cancer cells using monoclonal antibodies.
- We have shown that the monoclonal antibody E4G10, when coupled to an alpha-particle emitting isotope, selectively targets cells in newly formed tumor blood vessels. Our experiments in mice suggest that alpha-particle immunotherapy to tumor vasculature, alone or in combination with sequential chemotherapy, could be an effective approach to cancer therapy. PLoS One. 2007 Mar 7;2(3):e267. [PubMed Abstract]
- We have also developed a molecular nanogenerator that releases alpha particles inside cancer cells. Our initial clinical study of a CD33-targeted generator in leukemia patients shows that this therapeutic strategy is feasible and safe, and shows anticancer effects.
- We have demonstrated that it is possible to control the pharmacokinetics and therapeutic index of targeted antibodies pharmacologically by modulation of the neonatal Fc receptor protein. Our studies in mice indicate that this approach can yield an enhanced tumor contrast and reduction of normal-tissue toxicity for tumor imaging and therapy. J Clin Invest. 2007 Sep;117(9):2422-30. [PubMed Abstract]
- We are exploring ways to deliver drugs and other substances to tumors using antibodies appended to carbon nanotubes. Our investigators have shown that such constructs can be targeted to cancer cells in vitro and in a lymphoma mouse model, suggesting that in the future carbon nanotubes could provide a platform for drug delivery and imaging. J Nucl Med. 2007 Jul;48(7):1180-9. [PubMed Abstract]
- We have also shown that another type of genetically engineered T cell, which expresses a modified antigen receptor protein that mediates its targeting to B cells, can enhance antitumor activity in mice bearing tumors of human systemic acute lymphoblastic leukemia. Based on these and other preclinical findings, we are planning clinical trials in which engineered T cells will be employed in the treatment of chemotherapy-refractory chronic lymphocytic leukemia patients. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5426-35. [PubMed Abstract]
- We have found that the protein CD32B is highly expressed on the surface of plasma cells from patients with systemic light-chain amyloidosis (AL). The monoclonal antibody 2B6 can effectively target this protein in mouse tumor models and will hence be explored for therapeutic targeting of CD32B in AL patients. Blood. 2008 Apr 1;111(7):3403-6. [PubMed Abstract]
- Our investigators have identified three peptide epitopes in the protein WT-1, a promising immunotherapy target for many cancers, and demonstrated that these epitopes can stimulate active immune responses against mesothelioma and leukemia cell lines. Our results support a vaccination strategy that we are now investigating in patients with AML, mesothelioma, and lung cancer. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4547-55. [PubMed Abstract]
- In a recent study in patients with chronic lymphocytic leukemia who had not been treated previously, we found that the chemotherapy drugs fludarabine and cyclophosphamide and the monoclonal antibody rituximab, if administered sequentially, yield improvements in the patients’ quality of response as compared to sequential treatment with fludarabine and cyclophosphamide alone. J Clin Oncol. 2009 Feb 1;27(4):491-7. [PubMed Abstract]