Developing In Vivo CAR-T Therapies: Implications for Rheumatology and Oncology

At the 2025 American Society of Hematology Annual Meeting, Orna Therapeutics announced that their in vivo CAR platform (ORN‑252) yielded potent, antigen‑directed immune effects in preclinical studies and demonstrated translation‑ready activity for autoimmune indications.

ORN-252 produced peripheral and splenic B cell depletion at low microgram‑per‑kilogram dosing in a humanized lupus mouse model, with a directional reduction in anti‑dsDNA titers versus comparators. In nonhuman primates, the company reported complete peripheral and splenic depletion at 0.1 mg/kg with durable depletion and shifts in memory versus naïve B cell phenotypes on repopulation.

Compared with B cell–targeting biologics in similar models, ORN‑252 achieved faster, deeper B cell clearance alongside declines in serologic autoantibody measures—findings that support readiness to assess clinical activity in SLE.