NEO-100 Enhances Delivery Of Herceptin For Treatment Of Metastatic Breast Cancer In The Brain
Enhanced Brain Delivery And Therapeutic Activity Of Trastuzumab After Blood-Brain Barrier Opening By NEO100 In Mouse Models Of Brain-Metastatic Breast Cancer.
Authors: Weijun Wang† 1, Haiping He†5, Nagore I. Marín-Ramos1, Shan Zeng5, Steven D. Swenson1, Hee-Yeon Cho1, Jie Fu6, Paul M. Beringer4, Josh Neman3, Ligang Chen5, Axel H. Schönthal2, Thomas C. Chen1,3
The efficacy of human epidermal growth factor receptor 2-targeted therapies, such as humanized monoclonal antibody trastuzumab (Herceptin®, Roche), in patients with breast-to-brain cancer metastasis is hindered by the low permeability of the blood-brain barrier (BBB). NeOnc Technologies conducted an in vitro and in vivo study to look at the ability of NEO-100 to assist in delivering trastuzumab across the BBB in order to more effectively delivery the therapeutic to a tumor site.
The study showed that NEO-100 greatly increased trastuzumab penetration across both in vitro BBB delivery and in vivo intravenous deliveryresulting in brain tumor-selective accumulation of trastuzumab, without detectable presence in normal brain tissue, along with increased presence of immune cell populations. As a result it was determined that NEO100 facilitates brain tumor entry of trastuzumab and T-DM1 and significantly enhances its therapeutic efficacy, along with increased antibody-dependent immune cell recruitment.
† These authors contributed equally to this project
1Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, 2Department of Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, 3Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, 4Department of Clinical Pharmacy, University of Southern California, Los Angeles, California, USA, 5School of Pharmacy, University of Southern California, Los Angeles, California, USA., 6Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, China