Successful use of anti-CD19 CAR T cells in severe treatment-refractory stiff-person syndrome

Proc Natl Acad Sci U S A. 2024 Jun 25;121(26):e2403227121. doi: 10.1073/pnas.2403227121. Epub 2024 Jun 17.

Abstract

Treatment with autologous chimeric antigen receptor (CAR) T cells has emerged as a highly effective approach in neuroimmunological disorders such as myasthenia gravis. We report a case of successful anti-CD19 CAR T cell use in treatment-refractory stiff-person syndrome (SPS). To investigate clinical and immunological effects of anti-CD19 CAR T cell use in treatment-refractory SPS, a 69-y-old female with a 9-y history of treatment-refractory SPS with deteriorating episodes of stiffness received an infusion of autologous anti-CD19 CAR T cells (KYV-101) and was monitored clinically and immunologically for more than 6 mo. CAR T cell infusion resulted in reduced leg stiffness, drastic improvement in gait, walking speed increase over 100%, and daily walking distance improvement from less than 50 m to over 6 km within 3 mo. GABAergic medication (benzodiazepines) was reduced by 40%. KYV-101 CAR T cells were well tolerated with only low-grade cytokine release syndrome. This report of successful use of anti-CD19 CAR T cells in treatment-refractory SPS supports continued exploration of this approach in SPS and other B cell-related autoimmune disorders.

Keywords: B cell autoimmunity; CAR T cells; chimeric antigen receptor; neuroimmunological disorder; stiff-person syndrome.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antigens, CD19* / immunology
  • Female
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Receptors, Chimeric Antigen / immunology
  • Stiff-Person Syndrome* / immunology
  • Stiff-Person Syndrome* / therapy
  • T-Lymphocytes / immunology
  • Treatment Outcome

Substances

  • Antigens, CD19
  • Receptors, Chimeric Antigen