Science

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 TCR 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 human leukocyte antigen (HLA) / peptide antigen. Loss of HLA 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 achieved unprecedented efficacy in 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 be the smallest T-cell engaging format with extended serum half-life.

TriTAC Offers Distinct Advantages

  • Composed of three distinct binding domains
  • Small size for superior tumor penetration through (see figure)
  • Ultra-potent T cell recruitment for highly-specific, targeted killing  
  • Albumin binding for half-life extension allows for convenient dosing without potential liabilities associated with the Fc domain of regular antibodies
  • High stability and production from use of highly stable, single-domain proteins supports safety, efficacy and ease of manufacturing

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