T Cells Redefining Cancer Immunotherapies
T cells are recognized as the immune system’s most professional killer cells to combat virally infected and cancer cells. With new insights about how cancer cells escape our immune system, cancer immunotherapies are rapidly redefining how cancer is treated. T cell therapies represent the next wave of innovation in the fight against cancer.
T Cell Engagers Induce Tumor Killing Independent of MHC-PEPTIDE Recognition
T cell engagers, or T cell-engaging bispecific antibodies, is a new therapeutic modality in the fight against cancer. T cell engagers are engineered proteins that redirect T cells to attack targeted tumor cells. They work as adaptors that transiently connect T cells with their target cells for redirected tumor cell lysis.
Unlike most other immunotherapies, T cell engagers allow binding of T cells to tumor-associated antigens. This way, redirected lysis by T cells becomes independent of T cell receptor (TCR) specificity and recognition of major histocompatibility complex, or MHC, expression. Loss of MHC expression is a frequent mechanism by which cancer cells escape T cell recognition.
TriTAC – T Cell Engagers for Solid Tumors
The bi-specific T cell engager, Blincyto®, has shown promising therapeutic potential in clinical trials for the treatment of hematological malignancies such as acute lymphoblastic leukemia (ALL).
With its proprietary TriTAC® format (Tri-specific T Cell-Activating Construct), Harpoon is taking this modality to the next level.
This novel class of T cell therapeutics aims to achieve superior efficacy in penetrating solid tumors as an “off-the-shelf” T cell therapy.
TriTACs, which are comprised of three binding domains, are designed to have an extended serum half-life and be about one-third the size of a monoclonal antibody.
TriTAC Offers Distinct Advantages
Extended Half Life & Stability: Stable in bloodstream and long-serum half-life allows for convenient dosing (weekly)
Active at Low Levels of Antigen Expression: Does not require high levels of target antigen expression to engage T cells to kill disease cells
MHC Independence: Direct T cells to kill target cells independent of MHC expression with expectation for more durable therapeutic responses than MHC dependent approaches
Small Size & Tissue Penetration: Small size (see figure) expected to allow for faster diffusion into human solid tumor tissue
Conventional Manufacturing: “Off the shelf” T cell therapy with less complex manufacturing than personalized or cell-based therapies