Combination Targeting of Immunoliposomal Therapeutics in a Murine Model of B-cell Lymphoma

摘要

Ligand-mediated targeting is being widely explored as a means to increase the selective uptake of drugs and gene therapeutics by target cells. We are researching the treatment of B cell malignancies using lipid-based nanocarriers (liposomes) targeted via several different antibodies against B cell surface antigens. B cell malignancies are monoclonal and express the antigens CD19, CD20 and CD22. We treated an animal model of B-cell lymphoma (Namalwa) with individual immunoliposomal formulations of vincristine (VCR), targeted with anti-CD19, anti-CD20, or anti-CD22 (Fig. 1, A1-3), compared with mixtures of two, or all three, of the immunoliposomal formulations (Fig. 1B). Mixtures of immunoliposomes gave improved therapeutics over individual formulations, and single injections of mixtures targeted via the two internalizing antibodies, anti-CD19 and anti-CD22, resulted in long term survivors. On-going studies are investigating the therapeutic efficacy of targeting liposomal VCR with two or more antibodies attached to the same liposome (multi-targeted liposomes, Fig. 1C) versus mixtures of individual immunoliposomes (Fig. 1B).