Allogene Therapeutics Unveils Novel Approach to Generate Engineered AlloCAR T™ Cells to Control Immune Rejection at the Annual Meeting of the Society for Immunotherapy of Cancer

Promising Preclinical Data Highlights a Simple One-Step Gene Editing Strategy to Prevent the Rejection of AlloCAR T™ Cells by Host T Cells and NK Cells

• Cloaking Approach Demonstrates Superiority to B2M Knock Out in a Syngeneic In Vivo Model
• Proprietary Approach Is One of Several Next Generation Technologies Being Pioneered at Allogene to Control Rejection

Excerpt from the Press Release:

SOUTH SAN FRANCISCO, Calif., Nov. 10, 2022 (GLOBE NEWSWIRE) — Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer, today presented pre-clinical data on a novel approach to immune “cloaking” designed to protect AlloCAR T™ cells from rapid host rejection. The technology is designed to prevent AlloCAR T™ cells from being recognized by host T cells without triggering substantial natural killer (NK) cell rejection and while preserving CAR T cell function. The findings were presented today during a poster session at the 37^th Annual Meeting of the Society for Immunotherapy of Cancer (SITC).

The development of “off-the-shelf” (allogeneic) CAR T products that utilize cells from healthy donors have the potential to make CAR T therapies scalable and accessible to more patients. The effectiveness of allogeneic CAR T cells requires controlling immune rejection of allogeneic CAR T cells by the patient’s immune cells, namely T and NK cells. Allogene is currently developing ALLO-647, a lymphodepletion agent which targets host immune cells but not AlloCAR T™ cells, to enhance the window of CAR T engraftment, but is also investigating several novel strategies that may enhance the performance of allogeneic CAR T products by controlling immune rejection. This preclinical study evaluated an alternative approach to immune evasion by selectively targeting NLRC5 and RFX5, transcriptional regulators that control expression of HLA molecules. NLRC5 knockout avoids CD8 T cell mediated rejection and RFX5 knockout avoids rejection by both CD8 and CD4 T cells, allowing the possibility to avoid a broader spectrum of T cell-mediated rejection with just one edit, in contrast to alternative approaches that require two edits.

“We believe that novel approaches to cloaking may further increase the efficacy of off-the-shelf CAR T products through avoidance of immune rejection,” said Barbra Sasu, Ph.D. Chief Scientific Officer at Allogene. “As we look to deliver on the promise of AlloCAR T cell products, we are investigating several novel approaches to supplement or potentially even replace our current platform for immune rejection avoidance. The data presented today is promising, showing that knockout of NLRC5 and RFX5 reduced T cell rejection whilst minimizing NK cell rejection and without impacting CAR T cell performance.”

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