Anti-HLA antibodies in recipients of CD19 versus BCMA-targeted CAR T-cell therapy

• Published in: American journal of transplantation Vol. 23; no. 3; pp. 416 - 422
• Main Authors: Hill, Joshua A., Kiem, Erika S., Bhatti, Atif, Liu, Winnie, Keane-Candib, Jacob, Fitzpatrick, Kristin S., Boonyaratanakornkit, Jim, Gardner, Rebecca A., Green, Damian J., Maloney, David G., Turtle, Cameron J., Smith, Jodi M., Gimferrer, Idoia, Blosser, Christopher D., Jackson, Shaun W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2023
• Subjects: alloantibody; Antigens, CD19; B cell biology; B-Cell Maturation Antigen; B-Lymphocytes; clinical research/practice; Desensitization; Hematologic Neoplasms; Humans; immunosuppressant - fusion proteins and monoclonal antibodies: B cell specific; immunosuppression/immune modulation; Immunotherapy, Adoptive; organ transplantation in general; panel reactive antibody (PRA); solid organ transplantation; translational research/science; MM; ALL; IGRT; translational research/science; Desensitization; immunosuppression/immune modulation; organ transplantation in general; clinical research/practice; B cell biology; alloantibody; panel reactive antibody (PRA); BCMA; MBC; LLPC; MFI; cPRA; immunosuppressant - fusion proteins and monoclonal antibodies: B cell specific; CARTx; HCT; solid organ transplantation; HLA
• ISSN: 1600-6135; 1600-6143; 1600-6143
• DOI: 10.1016/j.ajt.2022.11.001

Antibodies against foreign human leukocyte antigen (HLA) molecules are barriers to successful organ transplantation. B cell–depleting treatments are used to reduce anti-HLA antibodies but have limited efficacy. We hypothesized that the primary source for anti-HLA antibodies is long-lived plasma cells, which are ineffectively targeted by B cell depletion. To study this, we screened for anti-HLA antibodies in a prospectively enrolled cohort of 49 patients who received chimeric antigen receptor T-cell therapy (CARTx), targeting naïve and memory B cells (CD19-targeted, n = 21) or plasma cells (BCMA-targeted, n = 28) for hematologic malignancies. Longitudinal samples were collected before and up to 1 year after CARTx. All individuals were in sustained remission. We identified 4 participants with anti-HLA antibodies before CD19-CARTx. Despite B cell depletion, anti-HLA antibodies and calculated panel reactive antibody scores were stable for 1 year after CD19-CARTx. Only 1 BCMA-CARTx recipient had pre-CARTx low-level anti-HLA antibodies, with no follow-up samples available. These data implicate CD19neg long-lived plasma cells as an important source for anti-HLA antibodies, a model supported by infrequent HLA sensitization in BCMA-CARTx subjects receiving previous plasma cell–targeted therapies. Thus, plasma cell–targeted therapies may be more effective against HLA antibodies, thereby enabling improved access to organ transplantation and rejection management. [Display omitted]