Development of Artificial Antigen Presenting Cells for Prostate Cancer Immunotherapy; Final rept. 1 May 2004-3 Apr 2007

摘要

While adoptive immunotherapy holds promise as a treatment for cancer, development of adoptive immunotherapy has been impeded by the lack of a reproducible and economically viable method for generating therapeutic numbers of antigen-specific CTL. The issues of reproducibility and cost, in large part, relate to the use of cellular dendritic cells (DC) for expansion of CTL. Underlying disease and pretreatment often affect the number of and efficacy of DC. Induction of DC takes time and is dependent on costly cytokine mixtures. Our preliminary data indicates that HLA-Ig complexes coupled to beads (HLA-Ig based artificial Antigen Presenting Complexes, aAPC) can induce and expand antigen-specific T cells and possibly be used to replace standard DC-based ex vivo expansion of CTL. Potential advantages of aAPC over cellular DC not only relate to the variability in function and viability of DC, but also using aAPC one can load all HLA complexes with the specific antigenic peptide(s) of choice, modulate the costimulatory signals, and enrich/sort for the antigen-specific cells of interest.