Enhancing the Efficacy of Dendritic Cell Vaccines by Tissue Conditioning
Abstract
The overall objective of this proposal has been to investigate the novel in situ immune modulation for enhancing the efficacy of cancer vaccines. The central hypothesis of the approach under investigation is that the ex vivo step of DC maturation as a necessary prerequisite for generating migratory DC capable of stimulating strong antigen-specific T cell responses can be replaced by an in vivo process termed "in situ priming". Based on preclinical and clinical data from our laboratory and others we hypothesized that the topical immunostimulant Imiquimod is a suitable agent that provides the necessary signals to facilitate DC maturation, migration and effective antigen presentation. Ultimately, the profound immune stimulation by antigen loaded DC would lead to strong tumor-specific immune response. "In situ priming" approach has many advantages comparing to conventional in vitro maturation including (1) that it recapitulates more closely the physiological conditions for DC maturation and hence may lead to a more desirable outcome, namely a more potent immune response, (2) that it eliminates an in vitro culture step, which in the setting of this patient-specific cell therapy protocol represents a considerable simplification, and (3) that in situ maturation obviates the dependence on expensive biological reagents used for ex vivo DC maturation. Our preliminary research findings formed the basis of this proposal to investigate the novel concept of in "in situ priming" in the setting of a phase I/II clinical study and to perform detailed immunological and molecular studies both of the local injection site and the peripheral blood stream to better understand the mechanisms of DC maturation and T-cell activation by antigen presenting cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2009
- Accession Number
- ADA509959
Entities
People
- Philipp Dahm
Organizations
- University of Florida