Harpoon Therapeutics Unveils ProTriTAC Platform: A Novel, Protease-Activated T Cell Engager Platform Designed to Access a Broad Landscape of Solid Tumor Targets
Harpoon Therapeutics, Inc. ("Harpoon"), a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body's immune system to treat patients suffering from cancer and other diseases, today presented preclinical data supporting the development of a new Protease-activated Tri-specific T cell Activating Construct ("ProTriTAC") platform. The new ProTriTAC platform is based on Harpoon’s Tri-specific T cell Activating Construct ("TriTAC™") technology, which is designed to bind a patient’s immune cells to cancer cells. This binding leads to activation of the immune cell, which then attacks and kills the cancer cell. Data were presented at the 2018 Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C., held November 9-11, 2018.
Therapeutics derived from the new ProTriTAC platform are intended to be administered as T cell inactive prodrugs and are optimized for serum exposure to ensure delivery to solid tumor tissues. At the site of the tumor, these prodrugs can be locally activated by tumor-associated proteases. This induces T cells to kill tumor cells expressing target antigen without affecting other tissues.
“We are very pleased to launch our ProTriTAC platform, which retains the advantages of our TriTAC platform, including activity at low levels of target expression, extended serum half-life and conventional manufacturing. Our ProTriTAC platform allows us to access tumor-associated antigens that have been historically challenging because they are expressed in both tumors and non-tumor tissues. ProTriTAC therapeutics are designed to be serum half-life extended, but do not engage T cells until they are clipped by tumor-associated proteases. Once clipped, a T cell activator is released at the site of the tumor. However, this T cell activator now has a short half-life and is quickly removed from circulation before it can impact non-tumor tissues,” said Holger Wesche, PhD, Chief Scientific Officer of Harpoon. “Harpoon plans to bring its first ProTriTAC product candidate into IND-enabling studies in 2019.”
“ProTriTAC is an important extension of Harpoon’s proprietary TriTAC platform, a T cell engager platform designed to harness the natural power of the patient’s own immune system to fight cancer and other diseases,” said Jerry McMahon, PhD, President and CEO of Harpoon. “ProTriTAC product candidates have the potential to increase the number of possible tumor antigen targets for Harpoon’s emerging pipeline.”
The poster entitled “ProTriTAC: A Protease-Activatable T Cell Engager Platform That Links Half-Life Extension to Functional Masking” can be found on the Publications page of Harpoon’s website. Key proof-of-concept data include:
Biological Activity Dependent on Protease Activation
Intact ProTriTAC proteins can block binding to T cells by more than 500-fold, but they can become fully active after a single proteolytic cleavage event, enabling T cell binding and activity in the tumor microenvironment.
Potent Anti-Tumor Activity In Vivo Is Protease-Dependent
When administered to tumor-bearing mice, ProTriTAC molecules can completely inhibit tumor growth with doses as low as 0.03 mg/kg. These data imply that this activity depends on proteolytic activation of the ProTriTAC in the tumor.
Reduced T Cell Binding and Rapid Clearance of the Active Drug in Non-Human Primates
Pharmacokinetic data derived from non-human primates confirm that ProTriTACs exhibit long serum half-life and support that T cells are not being engaged by the prodrug form.
About Harpoon Therapeutics
Harpoon Therapeutics is a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases. T cell engagers are engineered proteins that direct a patient’s own T cells to kill target cells that express specific proteins, or antigens, carried by the target cells. Using its proprietary Tri-specific T cell Activating Construct (TriTAC) ™ platform, Harpoon is developing a pipeline of novel T cell engagers, or TriTACs, and is initially focused on the treatment of solid tumors and hematologic malignancies. Harpoon has also invented a ProTriTAC platform that applies a prodrug concept to TriTAC to create T cell engagers designed to be preferentially active in the tumor microenvironment.
For more information, please visit www.harpoontx.com.
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