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SEP 17, 2020 12:45 PM EDT

Stimuli-responsive Nanomaterials for Imaging Immunotherapy Response

Speaker
  • Institute for Applied Life Sciences, University of Massachusetts Amherst
    Biography
      Ashish Kulkarni is an Assistant Professor in the Department of Chemical Engineering at the University of Massachusetts Amherst. He has courtesy appointments in the Departments of Chemistry and Biomedical Engineering. Prior to this, he was an Instructor of Medicine at Harvard Medical School and Associate Bioengineer at Brigham and Women's Hospital. He received his B. Tech. in Chemical Technology from Institute of Chemical Technology, University of Mumbai, his PhD in Chemistry from University of Cincinnati, Ohio and his postdoctoral training from Harvard Medical School and MIT. At UMass Amherst, his lab is working on the development of nanoscale platform technologies for cancer immunotherapy applications. His work is published in high impact journals (including Advanced Materials, Nature Biomedical Engineering, Nature Communications, PNAS, ACS Nano, Biomaterials, Cancer Research etc.) and gathered a lot of attention and featured in several global media outlets (BBC News, Boston Globe, Boston Herald, Yahoo News, Nature, Science News, Science Daily etc.). He was recently selected as one of the top 12 rising researchers by American Chemical Society's Chemical & Engineering News, a 'Young Innovator' in Cellular and Molecular Bioengineering' by Biomedical Engineering Society and a 'NextGen Star' in Caner Research by American Association for Cancer Research. He is a recipient of the Melanoma Research Alliance Young Investigator Award, Cancer Research Institute Technology Impact Award, Hearst Foundation Young Investigator Award and Harvard Cancer Center Career Development Award.

    Abstract

    Immunotherapy such as immune checkpoint inhibitor antibodies have revolutionized the treatments for hard-to-treat cancers, with durable responses observed in clinics. However, the overall response is observed only in a small subset of patients. Also, immunotherapy induces delayed on-set of responses and novel patterns of the anti-tumor response which makes it challenging to identify patient responders and non-responders early on, often leading to undertreatment or overtreatment. To address these challenges, we engineered a ‘stimuli-responsive nanomaterial’ (SRN) that can not only deliver an immune checkpoint inhibitor to the tumor but also report back on its efficacy in real time. We rationalized that this could be achieved by a novel two-staged stimuli-responsive polymeric nanomaterial with well-defined ratio of an immunotherapy drug and a drug-function activatable imaging agent. To accomplish this, we engineered a stimuli-responsive nanomaterial which comprises of three building blocks: an immunotherapy drug (anti-PDL1 antibody), an enzyme activatable imaging agent and a polymeric backbone that holds both elements together. In preliminary studies, we observed that anti-PD-L1 antibody conjugated SRNs inhibited PD1-PDL1 interactions efficiently and induced T-cell mediated cancer cell apoptosis that can be imaged using activatable imaging probe. SRNs not only enabled real-time immunotherapy response imaging in tumor bearing mice but also distinguished between highly responsive and partially responsive tumors. Furthermore, increasing doses resulted in better response and enhanced sensitivity in partially responsive tumors. This study shows that the treatment with SRNs induced a potent anti-tumor immune response that can be directly imaged and is more effective in imaging response than current agents.


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