Current Pharmaceutical Design - Volume 15, Issue 23, 2009

Immunotoxins are anticancer agents with at least two functional components, one of which binds to a tumor-specific, internalizing cell-surface antigen and one that confers cellular toxicity. The two components may be joined covalently in vitro by chemical conjugation or they may be expressed as a fusion protein generated by recombinant DNA technology. The binding moiety is usually a monoclonal antibody derivativ Read More

Recombinant immunotoxins are proteins composed of fragments of monoclonal antibodies fused to truncated protein toxins. No agents of this class are approved yet for medical use, although a related molecule, denileukin diftitox, composed of interleukin-2 fused to truncated diphtheria toxin, is approved for relapsed/refractory cutaneous T-cell lymphoma. Recombinant immunotoxins which have been tested in patients with chem Read More

Ribonucleases degrade RNA, now considered an important drug target. The parent member of this protein superfamily is bovine pancreatic RNase A that functions as a digestive enzyme. Other physiological roles and activities have been ascribed to more recently discovered members of this superfamily. Angiogenin was isolated by following angiogenic activity from cell culture media conditioned by colon cancer cells. ONCONA Read More

Recombinant fusion proteins are an expanding, important class of novel therapeutic agents. The designs of these constructs typically involve a cell-targeting motif genetically fused to a highly toxic class of enzymes capable of ruthlessly attacking critical cellular machinery once delivered successfully to the cytoplasm of the target cell. Initial development of this class of constructs typically contained recombinant growth fa Read More

Certain characteristics of tumor cells make it possible to develop rational strategies for targeting tumors without harming normal cells. These include the presence of cell surface molecules that characterize the current state of the tumor (e.g. CD30 on Hodgkin lymphoma cells) and the genetic and epigenetic changes that activate oncogenes and inactivate tumor suppressor genes (e.g. the inactivation of tumor suppress Read More

Immunotoxins (ITs) are protein-based drugs combining a target-specific binding domain (usually derived from an antibody) and a cytotoxic domain to kill target cells. They are among the most promising new therapeutic tools to fight cancer, and several clinical trials have been completed with encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenge Read More

Immunotoxins are powerful tools to specifically eliminate deviated cells. Due to the side effects of the original immunotoxins, they were only considered for the treatment of cancer as in these cases, the potential favourable effect outweighed the unwanted toxic side effects. Over time, many improvements in the construction of immunotoxins have been implemented that circumvent, or at least strongly diminish, the sid Read More

Targeted delivery of cytotoxic agents limits the severe toxic side-effects of anti-cancer drugs on healthy tissues. Annexin A5 is a well explored probe to target phosphatidylserine (PS)-expressing cells in vivo. Our novel understanding of the cellular and molecular mechanism of annexin A5 as a cell-entry agent and the finding that PS is expressed on living tumour as well as endothelial cells in the tumour vasculature, will allow the dev Read More

Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drugcontact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery Read More

The aetiology of obesity is multi-factorial. Recent research has identified a novel association between endotoxaemia (circulating lipopolysaccharide in the systemic circulation) and low-grade inflammation in the adipose organ, which may contribute to obesity. The mechanisms for the low-grade elevation of circulating lipopolysaccharide in obesity are poorly understood. Vitamin D has been increasingly recognised for its pleiotropi Read More