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MAY 02, 2017 8:00 AM PDT

Counteracting tumor evasion of antibody immunity, free webinar and Q&A session

Sponsored by: Abcam
Speaker
  • Professor of Molecular Medicine, Robert A. Welch Distinguished University Chair in Chemistry; Director, Texas Therapeutics Institute University of Texas Health Science Center at Houston
    Biography
      Dr. Zhiqiang An is Professor of Molecular Medicine, the Robert A. Welch Distinguished University Chair in Chemistry, and Director of the Texas Therapeutics Institute at the University of Texas Health Science Center at Houston. His laboratory focuses on cancer antibody drug resistance mechanisms, biomarkers for cancer therapeutic antibodies, and antibody drug discovery targeting cancer and infectious diseases. Dr An also directs the Therapeutic Monoclonal Antibody Lead Optimization and Development Core Facility funded by the Cancer Prevention and Research Institute of Texas (CPRIT).

      Previously, Dr. An served as Chief Scientific Officer at Epitomics, Inc. and was Director of Biologics Research at Merck Research Laboratories. He is a fellow of Society for Industrial Microbiology and Biotechnology, and is well published in the field of antibody drug discovery, including the award-winning book "Therapeutic Monoclonal Antibodies: from Bench to Clinic".

      Dr An started his biotech career at Millennium Pharmaceuticals. He received his Ph.D. degree from the University of Kentucky and his postdoctoral training at the University of Wisconsin-Madison.

    Abstract

    DATE: May 2, 2017
    TIME: 8:00am PT, 11:00am ET, 4:00pm GMT, 5:00pm CET

    The natural immune responses that patients develop to their own tumors, as well as therapeutic regimens employing the latest anti-cancer monoclonal antibodies, would reasonably be expected to suppress tumor growth. Yet, a perplexing resistance to both is widespread. The ineffectiveness of the immune system to prevail in these situations suggests that cancers possess tactics to evade antibodies that could otherwise eradicate them. 

    With a clinical context in mind, we observed that tumor-associated protein-degrading enzymes can diminish, and in some cases negate, cell killing functions by inducing a single clip in a small part of the antibody structure. The structural modification is so subtle that it had not been previously recognized and would not have been anticipated to so profoundly impair the antibody. To be able to visualize and establish if such cleavage occurred in cancer, we had to develop innovative antibodies for that exact purpose. 

    The new antibodies readily enabled the visualization of antibody damage when incubated with cancer cells in the laboratory or within tumor tissues obtained from animals or human patients - more importantly - the same antibody tools possessed the additional and remarkable property of restoring the lost functions to the damaged antibodies. The “rescue” of lost function suggested that this could be exploited as a therapy in cases where tumors cause antibody damage in order to evade our immune system. This novel therapeutic strategy represents a potentially new direction in cancer immunotherapy.

    This webinar will review:

    • A minor proteolytic cleavage at IgG hinge greatly impairs the effector functions of anticancer antibodies
    • Proteolytic hinge cleavage of IgGs as a mechanism of tumor evasion of antibody-based immunity
    • The potential of “rescue” of lost IgG Fc function as a novel therapeutic strategy for cancer

    Learning Objectives:

    • Review mechanisms of tumor cells used to evade interaction from anti-cancer antibodies 
    • Learn how antibody technology can be used to develop antibodies capable of visualizing subtle, specific modifications
    • Learn about a potential novel cancer therapeutic method of ‘’restoring’’ antibodies damaged by tumor-associated protein-degrading enzymes

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