RESUMO
Antibody-drug conjugates (ADCs) are a novel modality that allows targeted delivery of potent therapeutic agents to the desired site. Herein we report our discovery of NAMPT inhibitors as a novel nonantimitotic payload for ADCs. The resulting anti-c-Kit conjugates (ADC-3 and ADC-4) demonstrated in vivo efficacy in the c-Kit positive gastrointestinal stromal tumor GIST-T1 xenograft model in a target-dependent manner.
RESUMO
Inflammation is an immune response that marks several pathophysiological conditions in our body. Though adaptive immune cells play a major role in the progression of the disease, components of innate immune system, mainly monocytes and macrophages play the central role in onset of inflammation. Tissue-associated macrophages are widely distributed in the body showing tremendous anatomical and functional diversity and are actively involved in maintaining the homeostasis. They exhibit different phenotypes depending on their residing tissue microenvironment and the two major functional phenotypes are classically activated M1 phenotype showing pro-inflammatory characteristics and alternatively activated M2 phenotype demonstrating anti-inflammatory nature. Several cytokines, chemokines and other regulatory mediators delicately govern the balance of the two phenotypes in a tissue. This balance, however, is subverted during infection, injury or autoimmune response leading to increased population of M1 phenotype and subsequent chronic inflammatory disease states. This review underlines the role of macrophages in inflammatory diseases with an insight into potential molecular targets for nucleic acid therapy. Finally, some recent nanotechnology-based approaches to devise macrophage-specific targeted therapy have been highlighted.
