Julia Y. Ljubimova
Cedars-Sinai Medical Center, USA
Ljubimova J. Y is a Professor and Director of Nanomedicine Research Center at the Department of Neurosurgery at Cedars-Sinai Medical Center. She works on clinical and basic cancer research in her entire career. The major interest is the differential cancer gene expression as a tool for finding novel/early markers of cancer development, and for working out new nanomedicine drugs against these tumor targets for treatment and/or imaging. One of the novel markers, the structural tumor vessel wall protein laminin-411, is currently in a clinical trial as a prognostic and diagnostic marker for human glial tumor progression. These discoveries led to the development of new technologies for drug delivery and engineering of the new class of anti-cancer nanomedicine drugs. Currently her research is supported by three NIH/NCI, private and industry grants. She is the author of over 70 publications, reviews and book chapters as well as an inventor on nine patents and patent applications.
Nanopolymers are highly promising vehicles for multi-targeting and can provide molecular combination therapy and thus, personalized therapy based on specific marker expression profiles. In our work, a natural nanobiopolymer, polymalic acid (PMLA), was used as a nanoplatform for the family of PolycefinTM drugs to treat primary and metastatic tumors. Treatment efficacy was examined in treatment of primary brain and breast and metastatic tumors with polymer-attached antisense oligonucleotides (AON) to four molecular markers: α and β laminin, EGFR, HER2 and tumor-specific corresponding monoclonal antibodies (mAb) to either EGFR (cetuximab) or HER2 (herceptin), and transferrin receptor (TfR) for delivery through mouse endothelial system including brain blood and tumor barriers (BBB/BTB). In brain tumors treated with polycefin nanobiopolymer bearing AON against chains of tumor vascular protein, laminin-411, the vascular area was significantly decreased and tumor size was reduced 10-fold. For HER2-positive primary breast cancer, more than 90% growth inhibition was achieved in vivo in a mouse model using polycefin-attached HER2 AON. Treatment of primary TNBC by another Polycefin version, where PMLA had anti-TfR mAb for transcytosis, nucleosome-related antigen binding 2C5 mAb for tumor cell targeting, and anti-EGFR AON to block tumor cell growth, also led to a significant reduction of tumor size. Polymer-treated tumors exhibited significant cell apoptosis identified by the cleaved PARP method. Polycefin drugs were also used to treat brain metastases. Animal survival after Polycefin treatment of lung metastasis, HER2- positive breast cancer and TNBC was significantly: 65% for lung cancer, 47% for HER2-positive breast cancer, and 81% for TNBC. Overall, these nanoconjugates showed significant anti-tumor activity to treat primary cancers and metastases to the brain.