AUG 26, 2020 8:00 AM PDT

Bio-Layer Interferometry as a strategic platform to validate covalent "proximity inducing" small molecules with synthetic tumor Immunotherapeutic applications

Sponsored by: Sartorius
C.E. Credits: P.A.C.E. CE Florida CE
Speakers
  • Assistant Professor-Chemical Immunology, Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, Department of Chemistry and Chemical Biology, McMaster University
    Biography
      Professor Rullo obtained scientific training and experience in several aspects of organic synthesis and carbohydrate chemistry, physical biochemistry, and immunology. After obtaining an undergraduate in Biochemistry from McMaster University, he engaged in structural carbohydrate chemistry and polysaccharide vaccine development with Dr. Mario A. Monteiro during his master's studies. As a doctoral student under the supervision of Dr. Mark Nitz at the University of Toronto, he developed fluorescent chemical probes of complex glycosaminoglycan binding interactions, in addition to new bio-orthogonal affinity labelling strategies. Dr. Rullo conducted his postdoctoral research in Dr. David A. Spiegel's laboratory at Yale University working to develop new small molecule based anti-cancer immunotherapeutic approaches. His research yielded the discovery of first in class antibody recruiting molecules capable of targeting highly metastatic cancers in vivo. His laboratory is currently initiating three platforms engaging both basic molecular science and translational cancer therapeutic research on the interface of chemistry and tumor immunology. These platforms are focused on the design of "proximity inducing" covalent and multivalent chemical tools to interrogate immune activation mechanisms, and the development of new synthetic molecule based tumor immunotherapeutic targeting strategies.

      The Rullo Lab https://www.rullolab.com/
      Dr Rullo's Pubmed publications https://pubmed.ncbi.nlm.nih.gov/?term=Anthony+Rullo
      Additional publications https://pubmed.ncbi.nlm.nih.gov/?term=Rullo+A;+Rullo+AF
    • Marketing Applications Manager, ForteBio
      Biography
        Nilshad Salim is a Marketing Applications Manager at ForteBio, and has been with the company since 2016. Nilshad is responsible for identifying, developing, and validating emerging applications and workflow solutions that enhance our label-free portfolio. His work focuses on several vertical markets including antibody discovery, cell line development, and biomolecular interaction analysis. Prior to joining ForteBio, he held postdoctoral research roles in the areas of virology and cancer biology at Indiana University School of Medicine, and the University of Kansas Medical Center. Nilshad obtained his Ph.D. in biochemistry from Wayne State University in 2011.

      Abstract
      DATE:  August 26, 2020
      TIME:   8:00am PDT, 11:00am EDT
       
      The host immune "recognition" of cancer forms the basis of modern tumor immmunotherapy, a highly targeted treatment option with the demonstrated ability to "cure" previously lethal blood cancers. Immune recognition is mimimally governed by the proximity of "active" phagocytic and cytotoxic immune cells to the site of target cancer cells. To probe mechanistic aspects of the recognition process, generate useful immunotherapeutic design principles, and design potentially new classes of "reactive" synthetic tumor immunotherapeutics, our lab develops chemical tools that modulate the proximity of host immune cells with cancer cells. One class of these chemical tools we call "covalent immune recruiters" or CIRs, function by binding and forming selective irreversible linkages to tumor antigens highly expressed on the cancer cell surface, and or natural immune machinery e.g. serum antibodies, Fc receptors. In vitro validation of CIR function is thus highly non-trivial as both binding affinities and covalent reaction kinetics must be characterized and differentiated in the context of two different proteins.
       
      This seminar focuses on the unique suitability and application of BLI for the characterization of CIR function at the molecular level. We demonstrate BLI can be employed to efficiently characterize CIR binding affinities against both prostate tumor antigen and human serum antibody proteins, and selective covalent recruitment of these antibodies to the tumor antigen. The elucidation of these highly relevant physical parameters via other conventional techniques such as ITC and fluorescent polarization is difficult if not impossible largely due to higher sample concentration and time requirements, in addition to aggregation induced artifacts. Taken together, BLI validation of CIRs can accelerate lead compound advancement to in vivo validation studies with additional utility in characterizing emerging classes of covalent inhibitor drugs and ABPP chemical tools.
       
      Learning Objectives:
      • How to design, optimize, and validate a novel trifunctional chemical tool named covalent immune recruiters (CIRs) that can selectively label serum antibodies and direct immune responses to specific target proteins.
      • Use of Octet label-free binding analysis platforms to obtain kinetic information to quantify covalent labeling of antibodies and evaluate selectivity, also providing a 1 step solution to simultaneously monitor target protein binding and antibody recruitment under relevant equilibrium conditions.
      • Validation of CIRs specificity and selectively in vivo conditions.
       
      Webinars will be available for unlimited on-demand viewing after live event.
       
      LabRoots is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. ® Program. By attending this webinar, you can earn 1 Continuing Education credit once you have viewed the webinar in its entirety.

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