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

2023; Elsevier BV; Volume: 23; Issue: 3 Linguagem: Inglês

10.1016/j.ajt.2022.11.001

1600-6143

Joshua A. Hill, Erika S. Kiem, Atif Bhatti, Winnie Liu, Jacob Keane-Candib, Kristin Fitzpatrick, Jim Boonyaratanakornkit, Rebecca Gardner, Damian J. Green, David G. Maloney, Cameron J. Turtle, Jodi M. Smith, Idoia Gimferrer, Christopher D. Blosser, Shaun W. Jackson,

Biosimilars and Bioanalytical Methods

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 CD19