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Therapeutic Antibodies Need To Interact With Fc Receptors
Extended Abstract: 095-NHL-08
Therapeutic Antibodies Need To Interact With Fc Receptors Introduction
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.
Ronald Levy, MD Stanford University, Stanford, CA, USA [email protected]
We know that ADCC is an important mechanism of action of many antibodies that target the tumor, such as rituximab, trastuzumab and cetuximab, and several reports have shown that Fc competence is necessary for the action of antibodies that address the immune system, such as Ipilimumab, anti OX40, anti GITR and anti ICOS. 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.
Keywords Antibody, ADCC, Checkpoint, OX40, Vaccine S176
Therapeutic Antibodies Need To Interact With Fc Receptors Introduction
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.
Ronald Levy, MD Stanford University, Stanford, CA, USA [email protected]
We know that ADCC is an important mechanism of action of many antibodies that target the tumor, such as rituximab, trastuzumab and cetuximab, and several reports have shown that Fc competence is necessary for the action of antibodies that address the immune system, such as Ipilimumab, anti OX40, anti GITR and anti ICOS. 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.
Keywords Antibody, ADCC, Checkpoint, OX40, Vaccine S176