Ligand-targeted liposomal small molecule drugs and gene medicines are growing in popularitiy as a means of increasing the specific intracellular delivery of therapeutics to diseased cells.  The therapeutic outcome of targeted nanomedicines appears to be positively correlated with the antigen or receptor density at the disease cell surface.  Using a human B cell lymphoma murine xenograft model (5 x 106 Namalwa cells), we have explored the strategy of increasing the apparent receptor density on diseased cells by targeting to two or more surface antigens/receptors. Whole antibodies or Fab' antibody fragments against various combinations of anti-CD19, anti-CD22 (internalizing) or anti-CD20 (non-internalizing) were conjugated to formulations of liposomal vincristine (L-VCR), and mice were treated with mixtures of mono-targeted liposomes or multi-targeted liposomes.  Multi-targeted liposomes resulted in very high percentages of long term survivors in mice following a single treatment with one-sixth of the maximum tolerated dose of L-VCR.

Multi-targeted combinations of liposomal drugs for cancer chemotherapy

240th National Meeting (2010)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.