14 November 2018 - - US-based immunotherapy company Harpoon Therapeutics, Inc presented preclinical data supporting the development of a new Protease-activated Tri-specific T cell Activating Construct platform, the company said.

The new ProTriTAC platform is based on Harpoon's Tri-specific T cell Activating Construct 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 annual meeting in Washington, DC, held November 9-11, 2018.

Therapeutics derived from the new ProTriTAC platform are intended to be administered as T cell inactive prodrugs and are optimised 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.

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.

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.