Soluble Formats for Therapeutic Applications

Efforts in creating bispecific T cell engagers based on innate immune receptors are at the forefront of leveraging the unique capabilities of immune cells for targeted cancer therapy.

This innovative approach seeks to design cell-free immune therapies, aiming to refine and enhance the efficiencies of immune therapeutic leads. Bispecific T cell engagers (BiTEs) represent a groundbreaking class of cancer immunotherapy that binds simultaneously to cancer cells and T cells. By doing so, they bring the cancer cells into close proximity with the immune cells, facilitating the immune system's ability to recognize and destroy cancer cells more effectively.

Within the realm of these advanced therapeutic strategies, our team is dedicated to the development of a novel bispecific molecule, known as GAB (Gamma Delta TCR Anti-CD3 Bispecific molecule). GAB is a cutting-edge bispecific format that combines the targeting precision of gamma delta (γδ) T cell receptors (TCRs) with the potent activation capabilities of anti-CD3 antibodies. The γδ TCR component is specifically designed to recognize and bind to antigens present on the surface of cancer cells, while the anti-CD3 component engages T cells, activating them to exert cytotoxic effects against the tumor. This dual targeting mechanism ensures that T cells are directed precisely to tumor sites, enhancing the specificity and efficacy of cancer cell eradication.

The creation of GAB exemplifies our commitment to pushing the boundaries of cancer immunotherapy. By harnessing the innate recognition and direct killing capabilities of γδ T cells, combined with the proven effectiveness of T cell activation via CD3 engagement, GAB represents a new bispecific format with the potential to offer significant advantages over existing therapies. These include improved targeting of tumor cells, reduced off-target effects, and the activation of a broad spectrum of the immune response against cancer.

 Moreover, the development of such bispecific molecules aligns with the broader goal of designing off-the-shelf immune therapies. Unlike cell-based therapies, which involve the genetic modification and reinfusion of patient's own immune cells, protein based approaches, like the GABs, offer the possibility of off-the-shelf availability, potentially reducing costs and treatment times for patients. This strategy also circumvents some of the logistical and technical challenges associated with cell-based therapies, such as the complexity of cell extraction, modification, and expansion.

References

·      Gamma delta TCR anti-CD3 bispecific molecules (GABs) as novel immunotherapeutic compounds. J Immunother Cancer 2021.

·      The making of multivalent gamma delta TCR anti-CD3 bispecific T cell engagers. Front Immunol. 2023