Liberate Bio Achieves First In Vivo CAR-M B-Cell Depletion in Non-Human Primates
核心洞察
Liberate Bio (搜索)'s in vivo CAR-M therapy (搜索) achieved greater than 99% depletion of circulating B cells (搜索) in non-human primates after two well-tolerated doses.
The study represents the first demonstration that CAR-modified monocytes (搜索) and macrophages (搜索) can mediate B-cell depletion in primates, establishing a new therapeutic pathway for autoimmune diseases.
CAR-M showed improved safety over CAR-T (搜索) approaches with transient cytokine increases resolving within 48 hours and less than 1% delivery to T cells.
Liberate Bio (搜索) has achieved a significant breakthrough in cell therapy by demonstrating the first successful in vivo CAR-M-mediated B-cell depletion in non-human primates. The biotechnology company's preclinical data, presented at the American Society of Gene and Cell Therapies' Advancing Cell and Gene Therapies for Cancer conference in Philadelphia, showed that their in vivo CAR-M therapy (搜索) achieved greater than 99% depletion of circulating B cells (搜索) after two well-tolerated doses.
Breakthrough in CAR-M Technology
This milestone represents the first demonstration that CAR-modified monocytes (搜索) and macrophages (搜索) (CAR-M) can mediate B-cell depletion in primates, establishing a new potential therapeutic pathway for immune system reset in autoimmune and B-cell-driven diseases. The achievement marks a foundational development in the field of in vivo cell therapy.
"This is a foundational milestone for the field of in vivo cell therapy," said Walter R. Strapps, Ph.D., Chief Scientific Officer of Liberate Bio (搜索). "By reprogramming monocytes (搜索) and macrophages (搜索) instead of T cells, we've shown that it's possible to deplete B cells (搜索) through an entirely new immune compartment—one that naturally traffics to both circulation and tissues while avoiding the excessive immune activation that limits current CAR-T (搜索) approaches."
Enhanced Safety Profile
The study revealed significant safety advantages over traditional CAR-T (搜索) approaches. Transient increases in cytokines, including IL-6 and TNF-α (搜索), were observed after each dose but resolved within 48 hours and showed no signs of T-cell proliferation. Combined with less than 1% delivery to T cells, the results indicate that CAR-M may offer a safer in vivo reprogramming profile than CAR-T, with a reduced risk of cytokine release syndrome (搜索) (CRS) and ICANS (搜索).
The therapy demonstrated both potency and reversibility—an encouraging feature for therapeutic use in patients with moderate autoimmune disease who may not tolerate the intensity of CAR-T (搜索) therapy.
RAPTOR Platform Technology
Liberate Bio (搜索)'s proprietary RAPTOR™ platform directly screens lipid nanoparticles (搜索) (LNPs) in non-human primates to identify delivery vehicles that target extrahepatic immune cells. The lead LNP from this platform selectively delivered CAR-encoding mRNA to monocytes (搜索) and macrophages (搜索), producing the observed 99% B-cell depletion.
The RAPTOR™ platform combines high-throughput in vivo screening in non-human primates with AI-driven design and optimization, creating the first biological dataset powerful enough to train artificial intelligence on real delivery outcomes. This approach has enabled the company to engineer lipid nanoparticles (搜索) that target specific immune and bone marrow-resident cell types, including monocytes (搜索), macrophages (搜索), and hematopoietic stem cells (HSCs).
Clinical Development Timeline
Liberate Bio (搜索) plans to advance its first in vivo CAR-M candidate toward IND-enabling studies, with the goal of supporting the first clinical evaluation in the second half of 2026 through an investigator-initiated trial. This milestone will mark the transition of Liberate's platform from preclinical validation to human proof-of-concept, advancing a new therapeutic class designed to reprogram immune cells in vivo safely.
The company's initial clinical focus will include autoimmune indications, such as systemic lupus erythematosus (搜索) and multiple sclerosis (搜索), as well as oncology programs, including relapsed/refractory multiple myeloma (搜索) (rrMM), where malignant B cells (搜索) persist in circulation and bone marrow.
Therapeutic Potential
"In vivo CAR-M opens the door to treating millions of patients who have been beyond the reach of traditional cell therapy," said Shawn P. Davis, Ph.D., Chief Executive Officer of Liberate Bio (搜索). "We envision a future where immune programming can be performed safely, repeatably, and at scale—extending the benefits of engineered cell therapies to autoimmune and oncology patients alike."
The approach enables the programmable delivery of mRNA, gene editing, and other payloads directly to the cells that drive disease, unlocking the potential to treat oncology, autoimmune, and rare genetic disorders from within the body. Longer term, the company's platform provides a foundation for a new class of AI-informed, systemically delivered genetic medicines that extend to multiple organs and therapeutic areas.