Chimeric antigen receptor T cells against the IGHV4-34 B cell receptor specifically eliminate neoplastic and autoimmune B cells

Current US Food and Drug Administration–approved chimeric antigen receptor (CAR) T cell therapies for B cell leukemias and lymphomas target CD19, which is widely expressed across the B cell lineage, often leading to on-target, off-tumor B cell depletion, prolonged immune suppression, and antigen-negative escape in a subset of patients. In contrast, B cell receptor (BcR) signaling is essential for the survival of most mature B cell neoplasms, and BcRs carrying the immunoglobulin heavy variable gene IGHV4-34 are highly enriched in B cell malignancies compared with normal B cells. Further, self-reactive IGHV4-34 + serum autoantibodies are enriched in aggressive systemic lupus erythematosus (SLE) and other…

• CF
  Center for High Performance Computing, Shanghai Jiao Tong University
• LR
  Lymphoma Research Foundation
• HC
  Hairy Cell Leukemia Research Foundation
• LA
  Leukemia and Lymphoma Society
• FN
  Frederick National Laboratory for Cancer Research

  Award: 75N91019D00024
• AI
  Associazione Italiana per la Ricerca sul Cancro

  Award: 21198
• CF
  Colton Foundation
• DF
  DKMS Foundation