Leukemia-specific delivery of mutant NOTCH1 targeted therapy

Specific targeted therapy of chronic myelogenous leukemia with imatinib.

Chronic myeloid leukemia (CML) is characterized by the Philadelphia translocation that fuses BCR sequences from chromosome 22 upstream of the ABL gene on chromosome 9. The chimerical Bcr-Abl protein expressed by CML cells has constitutive tyrosine kinase activity, which is essential for the pathogenesis of the disease. Imatinib, an ATP-competitive selective inhibitor of Bcr-Abl, has unprecedent...

Production and Evaluation of Specific Single-Chain Antibodies against CTLA-4 for Cancer-Targeted Therapy

Background:  Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-4 inhibits the growth of malignant tumor cells. Anti-CTLA-4 monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodi...

Lean: Targeted Therapy for Care Delivery.

Advances in cancer care have reached unprecedented milestones, but these achievements come at significantly high costs.1 Disorganized and uncoordinated care can harm patients and contributes to unsustainable expenses. The CMS Innovation Center is addressing these issues with financial incentives under the Oncology Care Model (OCM) umbrella that aims to provide higher quality and more coordinate...

Advances in Targeted Drug Delivery

A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors

Higher Notch signaling is known to be associated with hematological and solid cancers. We developed a potential immunotherapeutic monoclonal antibody (MAb) specific for the Negative Regulatory Region of Notch1 (NRR). The MAb604.107 exhibited higher affinity for the "Gain-of-function" mutants of Notch1 NRR associated with T Acute lymphoblastic Leukemia (T-ALL). Modeling of the mutant NRR with 12...