DailyUpdates 19th March 2004.  The cytokines, chemokines, and growth factors market has $90 billion revenue potential.  Cytokine-based research is revolutionizing the treatment of inflammatory, infectious, and neoplastic diseases. 

Now the therapeutic use of cytokines has converged on the field of anti-cancer dendritic cell technology. 

Dendritic cells are believed to play a critical role in antitumor immune responses. These cells are the most potent antigen presenting cells known, uniquely capable of inducing immunity to newly introduced antigens.  Normally, dendritic cells  reside as immature cells in peripheral tissues however under certain conditions they take up and process antigens and also undergo activation and maturation.  Mature cells prime specific CD4 and CD8 T cells to these antigens. Tumors however are characterized by the presence of immature dendritic cells that are unable to stimulate T cells.  Defects in dendritic cell maturation and activation may prevent effective antitumor responses and may even induce immune tolerance.

Activation and maturation of dendritic cells  ex vivo and their subsequent reinfusion to tumor-bearing recipients after a pulse with tumor antigen offers one approach to bypassing defects in the immune recognition and the destruction of tumors.  This process is however time consuming and costly.

In the March edition of the Journal of Clinical Investigation Furumoto et al report a recently developed approach which avoids the dependence on ex vivo dendritic cell activation and reinfussion of these cells.  Instead this Stanford University group have shown that increasing tumoral levels of the chemotactic chemokine, CCL20/macrophage inflammatory protein-3alpha (MIP-3alpha) stimulated the movement of endogenous dendritic cells into the tumor.  Increased tumoral levels were produced by forcing the tumor cells to express the chemokine or by injecting it directly into the tumor.  Stimulating the infiltration of dendritic cells in this fashion led to complete regression of colon tumors.  Stimulating the infiltration of dendritic cells also produced therapeutic immunity against melanomas although in this case intratumoral injection of CpG was required for therapeutic activity. 

These data demonstrate that the delivery of CCL20 protein alone or in combination with CpG offers new possibilities for the treatment of patients with accessible tumors.

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