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. Chen^1,3

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