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2017 Ross Prize in Molecular Medicine — Regulating Immunity: Fc Receptor Biology

2017 Ross Prize in Molecular Medicine — Regulating Immunity: Fc Receptor Biology

Monday, June 5, 2017, 12:30 PM - 5:30 PM

The New York Academy of Sciences, 7 World Trade Center, 250 Greenwich St Fl 40, New York

Presented By

 

The Ross Prize in Molecular Medicine was established in conjunction with the Feinstein Institute for Medical Research and Molecular Medicine to recognize biomedical scientists whose discoveries transformed the way medicine is practiced. The awardees are midcareer researchers who have made a significant impact in the understanding of human disease pathogenesis and/or treatment. Moreover, it is anticipated that they will continue to make profound advances in the general field of molecular medicine.

The 2017 Ross Prize in Molecular Medicine will be awarded to Dr. Jeffrey V. Ravetch for his vital discovery of the mechanism by which the specific structure of antibodies controls immune cell reactivity. This work unveils the fine line between normal immune responses—such as those that remove foreign pathogens—and autoimmunity; processes that govern countless diseases. Dr. Ravetch's work continues to elucidate the complex cellular signaling that governs this fulcrum of immunity, and it is with this knowledge that new therapies will be pursued.

Registration Pricing

General Admission: $5.00

Although on-site registration may be possible on the day of the event, pre-registration is highly encouraged due to space limitations.

Registration

Member
$5
Nonmember Academia, Faculty, etc.
$5
Nonmember Corporate, Other
$5
Nonmember Not for Profit
$5
Nonmember Student, Undergrad, Grad, Fellow
$5
Member Student, Post-Doc, Fellow
$5

Sponsors

This symposium is made possible by the generosity of Jack and Robin Ross with support from

Feinstein Institute for Medical ResearchMolecular Medicine

Promotional Partners

The Antibody Society

IAVI, the International AIDS Vaccine Initiative

The Infectious Diseases Society of New York

Inflammation Research Association

Agenda


Monday, June 05, 2017

12:30 PM

Registration and Refreshments

1:00 PM

Welcome and Introductory Remarks
Klas Kärre, MD, PhD, Karolinska Institutet
Jack and Robin Ross, The Feinstein Institute for Medical Research Board of Directors
Brooke Grindlinger, PhD, The New York Academy of Sciences

Session I: 2017 Ross Prize in Molecular Medicine Presentation and Lecture

1:30 PM

2017 Ross Prize in Molecular Medicine Announcement and Presentation
Klas Kärre, MD, PhD, Karolinska Institutet

1:40 PM

2017 Ross Prize in Molecular Medicine Acceptance
Jeffrey V. Ravetch, MD, PhD, The Rockefeller University

1:45 PM

Diversification of Antibody Effector Function
Jeffrey V. Ravetch, MD, PhD, The Rockefeller University

2:45 PM

Networking Coffee Break

Session II: The Future of Fc Receptor Biology

3:15 PM

Human Immune Responses to Ebola Virus Infection
Rafi Ahmed, PhD, Emory University

3:45 PM

Fc Receptor Interaction is Required for in situ Vaccination
Ronald Levy, MD, Stanford University

4:15 PM

Closing Remarks
Klas Kärre, MD, PhD, Karolinska Institutet

4:30 PM

Reception

Abstracts

Diversification of Antibody Effector Function
Jeffrey V. Ravetch, MD, PhD, The Rockefeller University

Antibodies produced in response to a foreign antigen are characterized by polyclonality, not only in the diverse epitopes to which their variable domains bind but also in the various effector molecules to which their constant regions (Fc domains) engage. Thus, while Fab-antigen interactions are crucial to the specificity of the antibody response, there is a crucial role for the Fc domain in mediating the diverse effector properties triggered by antigen recognition, even for processes traditionally attributed solely to recognition by the Fab, such as neutralization of toxins and viruses. Specific interactions of the IgG Fc domain with distinct receptors expressed by diverse immune cell types result in the pleiotropic effector functions for IgG, including the clearance of pathogens and toxins, lysis and removal of infected or malignant cells, modulation of the innate and adaptive branches of immunity to shape an immune response, and initiation of anti-inflammatory pathways that actively suppress immunity. The Fc domain mediates these diverse effector activities by engaging two distinct classes of Fc receptors (type I and type II) on the basis of the distinct conformational states that the Fc domain may adopt. These conformational states are regulated by the differences among antibody subclasses in their amino acid sequence and by the complex, biantennary Fc-associated N-linked glycan. I will discuss the diverse downstream proinflammatory, anti-inflammatory and immunomodulatory consequences of the engagement of type I and type II Fc receptors in the context of infectious, autoimmune, and neoplastic disorders.

Fc Receptors are Important for Passive and Active Immunotherapy
Ronald Levy, M.D., Stanford Medical School

When Rituxan, the first monoclonal antibody for the treatment of cancer was developed, it became clear that its mechanism of action involved the Fc receptor. We noticed that the likelihood of tumors to respond was greatly influenced by which of the two different forms of the Fc receptor gene (CD16) the patient had. One form was known to bind better to the Fc portion of the therapeutic antibody and patients who had this form had a higher tumor remission rate. This result was concordant with the now classical report by Clynes and Ravetch on the role of the Fc receptor (CD16) in the therapy of Rituxan against human tumors transplanted into mice.
 
More recently, we have realized that active vaccination against tumors, by in situ injection of immune enhancing antibodies, also depends completely on the ability of the antibodies to bind to the Fc receptor. This result might imply that the antibodies are depleting an inhibitory population of T cells through engagement of CD16 on NK killer cells, or that the antibodies are binding to an alternative Fc receptor (CD32) on macrophages thus allowing the antibodies to better stimulate the killer T cells within the tumor microenvironment.

Human Immune Responses to Ebola Virus Infection
Rafi Ahmed, PhD

Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 month after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

To view full attendee list, you must first register for the event, then log in to the Academy website. This list is provided for the personal, noncommercial and informational use only of event attendees, in a manner that is consistent with the New York Academy of Sciences’ mission, goals and activities.
  • Abbvie ABC

  • ABC Resource

  • Advanced Proteome Therapeutics Inc.

  • Aggamin LLC

  • Albany Medical College

  • Albert Einstein College of Medicine

  • Albert Einstein College of Medicine and Montefiore Medical Center

  • Asterand Bioscience

  • AstraZeneca

  • Autoimmune Center

  • BioScience Communications

  • BMS

  • Boehringer Ingelheim

  • Bristol Myers Squibb

  • Bristol Myers-Squibb

  • Bristol-Myers Squibb

  • Bristol-Myers Squibb Company

  • Bronx-Lebanon Hospital Center

  • Center for Therapeutic Innovations, Pfizer Inc

  • Century Innovaions

  • City University of New York

  • Columbia University

  • CSHL

  • Damon Runyon Cancer Research Foundation

  • Eli Lilly

  • Eli Lilly & Company

  • Eli Lilly and Company

  • Emory University

  • Feinstein

  • Feinstein Institute

  • Feinstein Institute for Medical Research

  • Feinstein Institute for Medical Research at Northwell Health

  • FIMR

  • GE Healthcare Life Sciences

  • Global HIV Vaccine Enterprise

  • Green Corsair Tech Labs Global TM

  • Hofstra Medical School/The Feinstein Institute

  • Hunter College

  • IAVI

  • Icahn School of Medicine at Mount Sinai

  • Icahn School of Medicine at Mount Sinani

  • Icahn School of Medicine, Mount Sinai

  • Inovio

  • Janssen Research & Development

  • Janssen Research & Development, LLC

  • Johnson & Johnson

  • Kadmon

  • Karolinska Institute

  • Liu

  • Long Island University

  • Memorial Sloan Kettering Cancer Center

  • microbiology

  • Microbiology and Immunology

  • Mount Sinai

  • Mount Sinai School of Medicine

  • MSKCC

  • new york academy of sciences

  • New York Medical College

  • New York University Langone Medical Center

  • New York University School of Medicine

  • Northwell

  • Northwell Health

  • Northwell Health / Feinstein Institute

  • Northwell Physician Partners

  • Novartis Retiree

  • NYMC

  • NYS institute for Basic Research in Developm. Disabilities

  • NYS Institute for Basic Research in Developmental Disabil

  • Office of Aging, Elizabeth NJ

  • P. Universidad Católica de Chile

  • Perlmutter Cancer Center

  • Pfizer

  • Pfizer Inc.

  • Regeneron

  • Regeneron Pharmaceuticals

  • Rockefeller University

  • Roivant Sciences

  • Signum Biosciences

  • SQI DIAGNOSTICS

  • Stanford University

  • Stony Brook University

  • Subito Science LLC

  • SUNY Downstate Medical Center

  • Taconic Biosciences

  • The Albert Einstein College of Medicine

  • The Feinstein Institute for Medical Res

  • The Feinstein Institute for Medical Research

  • The Feinstein Institute for Medical Reserach

  • The Icahn School of Medicine at Mount Sinai

  • The New York Academy of Sciences

  • The New York Academy of Sciences NYAS

  • The Rockefeller University

  • THOMPSON BIOTECHNOLOGY GROUP

  • Tracy Lab at the Feinstein Institute

  • Trillium Medical Ventures

  • Tulip Biolabs, Inc

  • University of cambridge