Allogene Therapeutics presents preclinical Dagger platform technology data

Allogene Therapeutics presented preclinical data highlighting the company's next generation Dagger platform technology at the Emerging Cellular Therapies at the Forefront of Cancer Immunotherapy Keystone Symposia in Banff, Alberta, Canada. The Dagger technology, first unveiled at the company's R&D Showcase in November 2022, is designed to resist rejection of AlloCAR T cells by the host immune cells, enabling a prolonged window of persistence during which AlloCAR T cells can expand and actively target and destroy cancer cells. Dagger is a component of Allogene's anti-CD70 product candidate ALLO-316, which is being evaluated in TRAVERSE, a Phase 1 study of patients with relapsed/refractory renal cell carcinoma, or RCC. The Dagger platform arms AlloCAR T cells with a CD70-targeting receptor designed to recognize and deplete CD70 positive host cells while also masking the CD70 molecule expressed on the AlloCAR T cells themselves, preventing fratricide. CD70 is expressed on activated T cells and NK cells, and by selectively depleting alloreactive host cells, Dagger can potentially prevent the immune rejection of AlloCAR T cells. The results from these pre-clinical studies show that: A CD70 Dagger construct was optimized to selectively eliminate alloreactive T cells, enabling enhanced AlloCAR T cell survival in several in vitro models of rejection. Allogeneic CAR T cells expressing dual CD19 CAR and CD70 Dagger receptors demonstrated the ability to simultaneously kill CD19-positive tumor cells and resist rejection and fratricide. CD19 AlloCAR T cells armed with a CD70 Dagger were endowed with dual specificity and prevented CD19 antigen loss dependent escape by tumor cells in vitro and in vivo. The company has pursued an integrated strategy within Research and Development aimed at matching technology with insights obtained from the clinic to improve patient outcomes. In addition to ALLO-316, the company plans to deploy Dagger technology to enhance the persistence and activity of next generation AlloCAR T products.