GMP-compliant protocol for highly efficient generation of IL-12 secreting human DC
Reference Number TO 01-00683
The Challenge
Dendritic cells (DC) have a high potential as adjuvants in the induction of tumor-specific killer and helper cells in the patient. For this purpose, mature DC which have been maturated in vitro from immature DC are loaded with tumor-specific antigens and reinjected into the body. For therapy with DC it is essential that a sufficient number of mature DC are available. Since only 0.2% of white blood cells are DC it is necessary to have an efficient method for the in vitro production of mature DC. However so far, all these cells fail to produce efficient biological active IL-12, which is the most important factor for the induction of Th1 cells in the lymph nodes.
The Technology
At the Helmholtz Zentrum Munich a novel highly efficient GMP-compliant protocol for generation of mature human DC have been developed. The protocol is based on the finding that a TLR7/8 agonist is especially suitable for promoting the in vitro maturation of DC. The mature DC obtained by using the new protocol
• secrete significantly higher amounts of IL-12(p70)
• express significantly increased amounts of CCR7 chemokine receptors on their surfaces
• have an increased capacity to retain viable CD8+ T cells
• have a low adherence, therefore providing high yield
• augment the expression of co-stimulatory molecules.
Commercial Benefit and Opportunity
This new protocol allows for obtaining mature DC with improved and optimized immunostimulatory activity. The functional capacity of the mature DC populations to activate antigen-specific T cells is a crucial aspect of efficient T cell mediated immunity. Accordingly, this protocol enables the production of optimized and superior mature DC as an important tool for clinical purposes.
The technology is available for non-exclusive licensing. Parties interested in collaborative research and development are highly welcomed.
Developmental Status
The protocol has been widely used to generate mature DC with the capacity to be used in clinical settings. An in vivo proof-of-concept in mice has been successfully performed. A clinical phase I study using DC obtained with this protocol is in preparation.
Patent Situation
Patent applications are pending in EP (2004807), US, CA, and AU.
Relevant Publication
Zobywalski et al. (2007), J. Transl. Med. 5:18.
