DS-1055a: A Novel GARP-Targeting Immunotherapy for Solid Tumors

1. Executive Summary

DS-1055a is an investigational afucosylated human monoclonal antibody representing a novel approach in immuno-oncology. It is designed to selectively target Glycoprotein A Repetitions Predominant (GARP), a protein expressed on the surface of activated regulatory T cells (Tregs) within the tumor microenvironment. The primary mechanism of action of DS-1055a involves the depletion of these immunosuppressive GARP+ Tregs, thereby aiming to reverse tumor-induced immune tolerance and enhance the host's anti-tumor immune response. This therapeutic strategy is particularly relevant given the critical role Tregs play in inhibiting effective cancer immunosurveillance.

Developed through a collaboration between Daiichi Sankyo Co., Ltd. and BioInvent International AB, DS-1055a is currently undergoing Phase 1 clinical evaluation (NCT04419532) in patients with advanced or metastatic solid tumors. Preclinical studies have demonstrated its ability to deplete GARP+ Tregs and activate effector T cells, leading to significant anti-tumor activity in humanized mouse models. The afucosylation of DS-1055a is a key design feature intended to enhance its antibody-dependent cellular cytotoxicity (ADCC) capabilities, crucial for its Treg-depleting function. The development of DS-1055a signifies a focused effort to modulate the tumor microenvironment by specifically addressing Treg-mediated immunosuppression, offering a potentially complementary or alternative strategy to existing immunotherapies.

2. Introduction to DS-1055a

DS-1055a is emerging as a distinct investigational agent in the field of cancer immunotherapy, characterized by its unique molecular design and targeted approach.

2.1. Chemical and Therapeutic Classification