Dentritic Cell-Targeted Phage Vectors for Breast Cancer Vaccine

摘要

We hypothesize that one can use specific protein or peptide sequences to direct bacteriophage vectors to dendritic cells. We further propose that one can then use such retargeted phage vectors to deliver potentially important antigens to dendritic cells (DC), and that this may allow one to derive vectors capable of eliciting potent immune responses to breast cancer antigens such as her2. These hypotheses are being experimentally tested. During the period covered by this progress report, we have constructed modified lambda phage coat proteins which contain an array of receptor-binding/cell-targeting peptides which are expected to target receptors present on DC. Many of these have high affinities (nanomolar range) for their cognate ligands. We have also constructed modified lambda coat proteins which can be readily coupled to antibody molecules of interest, using engineered lgG binding domains. Finally, we have isolated SCFvs that interact with human DC-SIGN on an ELISA assay, and we have generated purified lambda phage particles which contain our modified coat proteins.