Liberate Bio, Inc., a biotechnology innovator advancing next-generation genetic medicines that deliver RNA therapies directly to immune cells, has announced groundbreaking preclinical data presented at the American Society of Gene and Cell Therapy’s (ASGCT) Advancing Cell and Gene Therapies for Cancer conference in Philadelphia. The results mark a major step forward in the emerging field of in vivo immune cell reprogramming, demonstrating for the first time that CAR-modified monocytes and macrophages (CAR-M) can successfully deplete B cells in non-human primates.
A New Frontier in Immune Cell Engineering
In this preclinical study, Liberate Bio’s in vivo CAR-M therapy achieved more than 99% depletion of circulating B cells following just two well-tolerated doses. According to the company, this is the first demonstration that CAR-modified monocytes and macrophages can effectively mediate B-cell depletion in a primate model. The achievement establishes a new therapeutic avenue for immune system “reset” approaches—offering potential treatments for autoimmune and B-cell–driven disorders that currently lack durable or well-tolerated therapies.
Transient increases in cytokines such as IL-6 and TNF-α were observed after each dose, but these effects resolved within 48 hours without evidence of T-cell proliferation or systemic toxicity. Moreover, less than 1% of the therapy was delivered to T cells, indicating that in vivo CAR-M therapies may offer a safer and more controlled reprogramming profile compared to CAR-T therapies. The data suggest a reduced risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS)—two of the most concerning side effects of T-cell–based therapies.
A Milestone for 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. “By reprogramming monocytes and macrophages instead of T cells, we’ve shown that it’s possible to deplete B cells through an entirely new immune compartment—one that naturally traffics through both circulation and tissues while avoiding the excessive immune activation that limits current CAR-T approaches.”
The implications are significant. Unlike T cells, monocytes and macrophages are innate immune cells capable of patrolling tissues, engulfing pathogens, and modulating inflammation. By targeting this cell population, Liberate Bio aims to harness a naturally homeostatic arm of the immune system to achieve potent yet transient immune modulation—without the prolonged and sometimes dangerous activation associated with T-cell therapies.
RAPTOR™ Platform: A Next-Generation LNP Discovery Engine
At the core of Liberate Bio’s innovation is its proprietary RAPTOR™ platform, a powerful discovery engine that directly screens lipid nanoparticles (LNPs) in non-human primates to identify vehicles capable of delivering RNA specifically to extrahepatic immune cells. Traditional LNPs have been limited by liver tropism, but RAPTOR enables selective targeting of monocytes and macrophages—unlocking a previously inaccessible delivery pathway.
The lead LNP identified through this platform successfully delivered CAR-encoding mRNA directly to monocytes and macrophages, resulting in the observed 99% depletion of B cells. Importantly, this depletion was both potent and reversible, an encouraging feature for clinical use. This reversibility could be critical for treating autoimmune diseases such as lupus or multiple sclerosis, where immune suppression must be controlled rather than permanent.
Expanding the Reach of Cell Therapy
“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. “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.”
Unlike ex vivo CAR-T or CAR-M approaches, which require cell extraction, genetic modification, and reinfusion under complex manufacturing conditions, Liberate’s in vivo platform uses systemic delivery of mRNA to reprogram immune cells directly within the body. This approach could enable repeat dosing, lower costs, and rapid scalability—transforming how genetic immunotherapies are developed and deployed.
Advancing Toward Clinical Translation
Following these promising preclinical findings, Liberate Bio plans to advance its first in vivo CAR-M candidate into IND-enabling studies. The company anticipates supporting the first clinical evaluation in the second half of 2026, initiated through an investigator-sponsored trial. This study will mark a pivotal transition for the company—from preclinical validation to human proof-of-concept—representing the next step in establishing in vivo immune cell reprogramming as a viable therapeutic modality.
Initial clinical efforts will focus on autoimmune disorders such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS), where controlled B-cell depletion can provide significant clinical benefit. Liberate also plans to explore applications in oncology, particularly for relapsed or refractory multiple myeloma (rrMM), where malignant B cells persist despite current therapies.
Pioneering a New Therapeutic Class
By successfully demonstrating CAR-M–mediated B-cell depletion in non-human primates, Liberate Bio has achieved a proof point that could redefine the boundaries of in vivo cell therapy. The data suggest that macrophage reprogramming could deliver the same therapeutic efficacy as CAR-Ts but with enhanced safety, reversibility, and scalability.
As the company prepares for clinical translation, this work positions Liberate Bio at the forefront of a new generation of immunotherapies—ones that can reprogram immune cells directly within the body, offering a potentially safer and more accessible approach to treating both autoimmune and malignant diseases.
With its RAPTOR™ platform, pioneering CAR-M technology, and ambitious clinical roadmap, Liberate Bio is leading the charge toward an era of programmable immunity—where the power of genetic medicine can be harnessed with precision, safety, and unprecedented reach.
