Generation of Tumor Targeted Dendritic Cell Vaccines with Improved Immunogenic and Migratory Phenotype

Abstract

Our group has employed methodologies for effective ex vivo generation of dendritic cell (DC) vaccines for patients with primary malignant brain tumors. In order to reliably produce the most potent, most representational vaccinated DC that will engender an antitumor response requires the ability to orchestrate multiple methodologies that address antigen cross-presentation, T-cell costimulation and polarization, and migratory capacity. In this chapter, we describe a novel method for augmenting the immunogenicity and migratory potential of DCs for their use as vaccines. We have elucidated methodologies to avoid the phenomenon known as immunodominance in generating cancer vaccines. We have found that culturing DC progenitors in serum-free conditions for the duration of the differentiation protocol results in a more homogeneously mature population of DCs that exhibit enhanced immunogenicity compared to DCs generated in serum-containing culture conditions. Furthermore, we demonstrate our method for generating high mobility DCs that readily migrate toward lymphoid organ chemoattractants using CCL3 protein. The combination of these two approaches represents a facile and clinically tractable methodology for generating highly mature DCs with excellent migratory capacity.

Dendritic cell therapy for neurospoagioma: Immunomodulation mediated by tumor vaccine

“…Notably, distinct modes of administration, including intradermal, subcutaneous, and venous delivery, can yield differing consequences. For instance, with intradermal and subcutaneous delivery approaches, DCs exhibit a tendency to migrate towards the draining lymph nodes, albeit with a relatively limited mobility, typically around 5% [ 73 ]. Conversely, when employing the vein delivery mode, DCs tend to accumulate within tissues and organs such as the liver, spleen, and kidney, albeit with relatively modest effectiveness [ 74 ].…”