We are conducting a Phase 1 prospective clinical trial assessing the feasibility and safety of treating subjects with progressive Multiple Sclerosis with chimeric antigen receptor T cells (CAR-T cells) with a CD-19+ glycoprotein binding site.

To assess the feasibility and safety of treating non-relapsing progressive phenotypes of Multiple Sclerosis with chimeric antigen receptor (CAR-T) immunotherapy with a CD-19+ binding site.

Phase 1 open label prospective study of a fully humanized CAR-T immunotherapy (KYV-101 Hu19-CD828Z) in a dose ranging 3 x 3 design for subjects with Multiple Sclerosis by 2017 McDonald criteria, with progressive worsening disease according to the 2014 Lublin phenotypic criteria. 12 subjects age 18-65 undergo apheresis, lymphodepletion, and infusion of autologously derived lentivirus engineered CAR-T/CD-19 cells at an initial dose of 33 million to 100 million cells IV with inpatient observation over 8 days with assiduous serological and clinical monitoring.

Study recruitment is  active and ongoing. Treated subjects to date have not experienced Cytokine Release Syndrome (CRS), Immune Effector Cell Associated Neurotoxicity (ICANS), or adverse events graded higher than CTCAE Version 5 Grade 1. We observed robust CAR-T cell expansion and CNS penetration. Correlative studies revealed changes in levels of various cytokines, interleukins and other immune markers over the course of post CAR-T treatment, with most pronounced changes indicative of peak immunomodulation detected at Day 14 post-infusion.