On February 1, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported preclinical data highlighting the Company’s next generation DaggerTM platform technology at the Emerging Cellular Therapies at the Forefront of Cancer Immunotherapy Keystone Symposia in Banff, Alberta, Canada (Press release, Allogene, FEB 1, 2023, View Source [SID1234626695]).
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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 (RCC).
"We are excited by the potential of this proprietary technology to enhance AlloCAR T cell function by preventing premature rejection of the cells while potentially reducing dependence on other lymphodepletion strategies," said Barbra Sasu, Ph.D., Chief Scientific Officer at Allogene. "The early clinical experience with ALLO-316 in advanced renal cell carcinoma suggests Dagger can meaningfully enhance AlloCAR T cell expansion and persistence. We are keen to apply this technology to other product candidates targeting both hematologic and solid tumors."
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.
About ALLO-316
ALLO-316, an AlloCAR T investigational product targets CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In March 2022, The U.S. Food and Drug Administration granted Fast Track Designation (FTD) based on the potential of ALLO-316 to address the unmet need for patients with difficult to treat RCC who have failed standard RCC therapies.