The unique chemical and functional properties of nanoparticles can be harnessed for the delivery of large quantities of various therapeutic biomolecules. Active targeting of nanoparticles by conjugating ligands that bind to target cells strongly facilitates accumulation, internalization into target cells and longer retention at the target site, with consequent enhanced therapeutic effects. Recombinant antibodies with high selectivity and availability for a vast range of targets will dominate the future. In this review, we systematically outline the tremendous progress in the conjugation of antibodies to nanoparticles and the clear advantages that recombinant antibodies offer in the therapeutic targeting of nanoparticles. The demonstrated flexibility of recombinant antibody coupling to nanoparticles highlights the bright future of this technology for modern therapeutic nanomedicine.

Mucin 1 antigen, highly expressed by epithelial ovarian cancer (EOC), is a potential target for immunotherapy. A previous successful phase 1 trial was conducted in patients with adenocarcinoma who were injected with Cvac, autologous monocyte-derived dendritic cells (DCs) incubated with mannosylated mucin 1 protein (M-FP). The present study was a phase 2 trial of Cvac in patients with advanced EOC.

Cell penetrating peptides (CPP), including the TAT peptide from the human immunodeficiency virus transactivator of transcription (HIV-TAT) protein and penetratin from Drosophila Antennapedia homeodomain protein, translocate various cargos including peptides and proteins across cellular barriers. This mode of delivery has been harnessed by our group and others to deliver antigenic proteins or peptides into the cytoplasm of antigen processing cells (APC) such as monocyte-derived dendritic cells (MoDC). Antigens or T cell epitopes delivered by CPP into APC in vivo generate antigen-specific cytotoxic T cell and helper T cell responses in mice. Furthermore, mice immunised with these peptides or proteins are protected from a tumour challenge. The functional properties of CPP are dependent on the various cargos being delivered and the target cell type. Despite several studies demonstrating superior immunogenicity of TAT and Antp-based immunogens, none has compared the immunogenicity of antigens delivered by TAT and Antp CPP. In the current study we demonstrate that a cytotoxic T cell epitope from the mucin 1 (MUC1) tumour associated antigen, when delivered by TAT or Antp, generates identical immune responses in mice resulting in specific MUC1 T cell responses as measured by in vivo CTL assays, IFNγ ELISpot assays and prophylactic tumour protection.