Session Speaker

Nanobioconjugate Engineering to Treat HER2/Neu Expressing Breast Tumors
Julia Y. Ljubimova
USA

HER2/neu targeting therapy is important to treat breast cancer. However, patients develop resistance to Herceptin (anti-HER2 antibody) and eventually die.

The new nanoconjugates engineered for a combined therapy of HER2/neu positive tumors by inhibiting angiogenesis, apoptosis and activating of innate and adaptive anti-tumor immune response. Nanobiopolymers had biodegradable and non-toxic polymalic acid platform with covalently conjugated anti-transferrin receptor antibody for transcytosis; antisense oligonucleotides (AON) to inhibit angiogenesis or induce apoptosis, and potent immunostimulatory antibody-cytokine fusion protein anti-HER2/neu IgG3-(IL-2). The anti-angiogenic effect was achieved using AONs inhibiting vascular tumor protein laminin-411 and apoptosis was induced by blocking HER2 mRNA. Polymer-recombinant fusion antibody-conjugate-IL-2 activities and mechanism of cell-delivery were evaluated.

In vivo anti-tumor activity was determined using syngeneic and xenogeneic nude mice with HER2 overexpressing mammary tumors. Intravenously administered Polycefin variant with AON to laminin-411 and anti-HER2/neu IgG3-(IL-2) caused significant 2-fold reduction of breast tumor size (p<0.05 vs. PBS) and 4-fold increase of animal survival (40% vs. 10%, p<0.05 vs. PBS control). Another Polycefin variant bearing anti-HER2 antibody and AON against HER2 caused 3.6-fold reduction in tumor size compared to Herceptin treatment (p<0.0001). A novel nanobiopolymer-based therapy may achieve significant clinical effect against HER2/neu overexpressing cancers.