Novel Immuno-Oncology Approach With Potential for Enhanced Antitumor Effect
NEW YORK, NY, USA I November 19, 2014 I Kadmon Corporation, LLC, today announced the presentation of preclinical data demonstrating the potential of a novel, bi-functional anti-PD-L1/IL-15 fusion protein, KD033, for the treatment of cancer. The data were presented in a poster session at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place in Barcelona, Spain.
Immune checkpoints act to modulate the immune system to maintain self-tolerance and resolve immune response. Cancer cells exploit these checkpoints, blocking the ability of the immune system to recognize and destroy tumor tissue. Antibody therapeutics that block the activity of the immune checkpoints CTLA4, PD-1 and PD-L1 have shown significant efficacy in clinical trials in several tumor types, resulting in rapid regulatory approvals. To enhance this activity, Kadmon has engineered a series of bi-functional proteins that not only inhibit immune checkpoint function, but also directly stimulate local anti-tumor immune responses.
The lead candidate from this effort, KD033, is a bi-functional fusion protein comprised of Kadmon’s proprietary anti-PD-L1 antibody linked at its tail to the cytokine IL-15 by the sushi domain of the IL-15 receptor. This combination brings together the benefit of inhibiting the PD-L1 immunosuppressive pathway and stimulating T-cell and NK (natural killer) cell activity via IL-15, all at the tumor site.
The data presented show that Kadmon’s proprietary anti-PD-L1 antibody completely blocks binding of PD-1 to PD-L1 and inhibits PD-L1-mediated suppressive effects on T-cell function. This activity is maintained in the bi-functional protein KD033. In addition, the data show that KD033 has significant IL-15 activity, stimulating the proliferation and cytotoxicity of CD8 T-effector cells, NK cells and NK1 cells in vitro. KD033 is stable and retains PD-L1 binding and blocking activity in serum and can be expressed at high levels in mammalian cells. In an animal model of lung cancer, the data show that the dual activity of the KD033 bi-functional protein results in increased survival of animals treated with KD033 when compared either to animals treated with an anti-PD-L1 antibody alone, or those treated with a non-tumor-targeted IL-15 fusion protein. The data also show a reduction of systemic IL-15 toxicities when using KD033.
“Combining a PD-L1 inhibitor with an IL-15 cytokine has the effect of removing the immune system’s anti-cancer brake and simultaneously stepping on its accelerator,” said Larry Witte, Ph.D., Executive Vice President, Research and Development at Kadmon. “The unique dual activity of a protein such as KD033 holds significant promise as a differentiated immuno-oncology therapeutic candidate. We look forward to advancing this candidate toward the clinic.”
About Kadmon Corporation
Kadmon Corporation, LLC, is a vertically integrated biopharmaceutical company focused on developing innovative products for significant unmet medical needs. We have a diversified product pipeline in oncology, monogenic diseases, immunological diseases and fibrosis, and metabolic disease. For more information, visit www.kadmon.com.
SOURCE: Kadmon
Post Views: 51
Novel Immuno-Oncology Approach With Potential for Enhanced Antitumor Effect
NEW YORK, NY, USA I November 19, 2014 I Kadmon Corporation, LLC, today announced the presentation of preclinical data demonstrating the potential of a novel, bi-functional anti-PD-L1/IL-15 fusion protein, KD033, for the treatment of cancer. The data were presented in a poster session at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place in Barcelona, Spain.
Immune checkpoints act to modulate the immune system to maintain self-tolerance and resolve immune response. Cancer cells exploit these checkpoints, blocking the ability of the immune system to recognize and destroy tumor tissue. Antibody therapeutics that block the activity of the immune checkpoints CTLA4, PD-1 and PD-L1 have shown significant efficacy in clinical trials in several tumor types, resulting in rapid regulatory approvals. To enhance this activity, Kadmon has engineered a series of bi-functional proteins that not only inhibit immune checkpoint function, but also directly stimulate local anti-tumor immune responses.
The lead candidate from this effort, KD033, is a bi-functional fusion protein comprised of Kadmon’s proprietary anti-PD-L1 antibody linked at its tail to the cytokine IL-15 by the sushi domain of the IL-15 receptor. This combination brings together the benefit of inhibiting the PD-L1 immunosuppressive pathway and stimulating T-cell and NK (natural killer) cell activity via IL-15, all at the tumor site.
The data presented show that Kadmon’s proprietary anti-PD-L1 antibody completely blocks binding of PD-1 to PD-L1 and inhibits PD-L1-mediated suppressive effects on T-cell function. This activity is maintained in the bi-functional protein KD033. In addition, the data show that KD033 has significant IL-15 activity, stimulating the proliferation and cytotoxicity of CD8 T-effector cells, NK cells and NK1 cells in vitro. KD033 is stable and retains PD-L1 binding and blocking activity in serum and can be expressed at high levels in mammalian cells. In an animal model of lung cancer, the data show that the dual activity of the KD033 bi-functional protein results in increased survival of animals treated with KD033 when compared either to animals treated with an anti-PD-L1 antibody alone, or those treated with a non-tumor-targeted IL-15 fusion protein. The data also show a reduction of systemic IL-15 toxicities when using KD033.
“Combining a PD-L1 inhibitor with an IL-15 cytokine has the effect of removing the immune system’s anti-cancer brake and simultaneously stepping on its accelerator,” said Larry Witte, Ph.D., Executive Vice President, Research and Development at Kadmon. “The unique dual activity of a protein such as KD033 holds significant promise as a differentiated immuno-oncology therapeutic candidate. We look forward to advancing this candidate toward the clinic.”
About Kadmon Corporation
Kadmon Corporation, LLC, is a vertically integrated biopharmaceutical company focused on developing innovative products for significant unmet medical needs. We have a diversified product pipeline in oncology, monogenic diseases, immunological diseases and fibrosis, and metabolic disease. For more information, visit www.kadmon.com.
SOURCE: Kadmon
Post Views: 51
