B-cells almost completely deleted in primates, company says
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Liberate Bio’s CAR-M cell therapy almost completely depleted B-cells in nonhuman primates, suggesting the approach may be used to treat B-cell diseases such as multiple sclerosis (MS) and some cancers.
The therapy is designed to genetically engineer monocytes and macrophages, two types of immune cells, to target and eliminate B-cells. That modification is done in vivo, or inside the patient’s body, eliminating the need to wait several weeks as seen with traditional cell therapies. It also doesn’t require patients to undergo chemotherapy to prepare for treatment.
The company said it plans additional studies that will support an investigational new drug application seeking clearance to begin clinical studies. The goal is to launch an investigator-initiated trial in the second half of 2026.
“CAR-M opens the door to treating millions of patients who have been beyond the reach of traditional cell therapy,” Shawn P. Davis, PhD, CEO of Liberate Bio, said in a company press release. “We envision a future where immune programming can be performed safely, repeatably, and at scale—extending the benefits of engineered cell therapies.”
The preclinical data were presented at the American Society of Gene and Cell Therapies’ Advancing Cell and Gene Therapies for Cancer conference, held Oct. 15-16 in Philadelphia.
MS is caused by the immune system mistakenly attacking healthy parts of the brain and spinal cord. B-cells are key immune cells involved in this attack, and they are also involved in certain blood cancers.
Researchers have been exploring T-cells, another immune cell type, as a potential approach to eliminating B-cells. T-cells can be engineered to produce a man-made receptor, called a chimeric antigen receptor (CAR), that recognizes a specific protein at the surface of disease-causing cells, making them extremely effective at eliminating those cells.
This approach is called CAR T-cell therapy, and it usually involves collecting the T-cells from patients, modifying them in the lab, and then introducing them back into the patient’s bloodstream to target B-cells.
Liberate Bio is developing a different kind of cell therapy that harnesses monocytes and macrophages instead of T-cells, and modifies the cells inside the patient’s body. This skips the cell collection and infusion steps and eliminates the need for a round of chemotherapy to prepare the body to receive the modified cells.
The company’s CAR-M therapy uses a messenger RNA (mRNA) molecule containing instructions to produce a CAR receptor targeting the CD20 protein in B-cells. mRNA is a temporary molecule used as a template to make proteins.
This mRNA molecule is inserted into lipid nanoparticles that target monocytes and macrophages, ensuring the therapy is directly delivered to these immune cells.
Researchers screened multiple nanoparticles in non-human primates using the company’s proprietary RAPTOR platform. After two doses, which were well tolerated, the lead nanoparticle, dubbed LNP LB01, led to a more than 99% depletion of B-cells.
After each dose, there was a transient increase in the levels of inflammatory molecules, including interleukin-6 and TNF-alpha, but these resolved within two days. Fewer than 1% of T-cells received the mRNA molecule from the lipid nanoparticle.
“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 to both circulation and tissues while avoiding the excessive immune activation that limits current CAR-T approaches,” said Walter R. Strapps, PhD, Liberate’s chief scientific officer.
The company’s initial clinical focus will include autoimmune diseases, such as MS and lupus, as well as multiple myeloma, a B-cell blood cancer.
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