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

Hill, Joshua A.; Kiem, Erika S.; Bhatti, Atif; Liu, Winnie; Keane-Candib, Jacob; Fitzpatrick, Kristin; 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.

doi:10.1016/j.ajt.2022.11.001

Cited by 10 publications

(9 citation statements)

References 30 publications

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“…A study of the fate of HLA allo-antibodies following CART-19 and CART-BCMA monotherapies was recently reported by Hill et al. 9 Consistent with our previous report and our data from mice, CART-19 had no effect on antibodies in 4/4 evaluable subjects. However, assessment of the fate of HLA antibodies after CART-BCMA monotherapy was not feasible.…”

Section: Discussionsupporting

confidence: 92%

“…However, we previously demonstrated that CART-19 does not deplete vaccine-induced protective antibodies as well as HLA allo-antibodies, 7 , 8 and this has been confirmed by others. 9 , 10 , 11 We tested this premise in a murine model of skin grafting that promotes robust allo-sensitization. C57BL/6J mice (B6) received two serial skin allografts from BALB/cJ donors (BALB/c).…”

Section: Resultsmentioning

confidence: 99%

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Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies

Zhang,

Markmann,

et al. 2023

Cell Reports Medicine

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies

Zhang,

Markmann,

et al. 2023

Cell Reports Medicine

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“…During a humoral immune response, plasma cells of varied lifespans are generated, with shortlived plasmablasts providing rapid antibody production in the acute phase and long-lived plasma cells sustaining durable antibody titers. While foreign antigen-specific long-lived plasma cells are known to persist for decades in humans [59][60][61] , the cellular phenotype of pathogenic plasma cells remains controversial. Since individual autoantibodies decline following therapeutic B cell ablation, despite a lack of CD19 and CD20 expression on plasma cells 27,62,63 , the prevailing model holds that the continuous generation of short-lived plasma cells from memory B cell precursors underlies the autoantibody repertoire 64 .…”

Section: Discussionmentioning

confidence: 99%

Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy

Bodansky,

Yu,

Rallistan

et al. 2023

Preprint

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The prevalence and burden of autoimmune and autoantibody mediated disease is increasing worldwide, yet most disease etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leverage advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of proteome-wide autoantibody profiles in both health and disease. We demonstrate that each individual, regardless of disease state, possesses a distinct set of autoreactivities constituting a unique immunological fingerprint, or “autoreactome”, that is remarkably stable over years. In addition to uncovering important new biology, the autoreactome can be used to better evaluate the relative effectiveness of various therapies in altering autoantibody repertoires. We find that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly alter an individual’s autoreactome, while anti-CD19 and CD-20 therapies have minimal effects, strongly suggesting a rationale for BCMA or other plasma cell targeted therapies in autoantibody mediated diseases.

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“…Recent data from Jackson et al. have shown that in patients with B‐cell malignancies who were also sensitized to HLA antigens, the use of CAR‐T specific for CD19 did not result in substantial reduction in HLA antibody levels 42 . The use of CAR‐T cells with specificity for BCMA may yield better results.…”

Section: Strategies For Desensitizationmentioning

confidence: 99%

Management of the sensitized pediatric renal transplant candidate

Puliyanda,

Jordan

2024

Pediatric Transplantation

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Kidney transplantation is the treatment of choice for patients with ESRD as it is associated with improved patient survival and better quality of life, especially in children. There are several barriers to a successful transplant including organ shortage, anatomic barriers, and immunologic barriers. One of the biggest immunologic barriers that precludes transplantation is sensitization, when patients have antibodies prior to transplantation, resulting in positive crossmatches with donor. 30%–40% of adult patients on the wait list are sensitized. There is a growing number of pediatric patients on the wait list who are sensitized. This poses a unique challenge to the pediatric transplant community. Therefore, attempts to perform desensitization to remove or suppress pathogenic HLA antibodies resulting in acceptable crossmatches, and ultimately a successful transplant, while reducing the risk of acute rejection, are much needed in these children. This review article aims to address the management of such patients both prior to transplantation, with strategies to overcome sensitization, and after transplantation with monitoring for allograft rejection and other complications.

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

Cited by 10 publications

References 30 publications

Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies

Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies

Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy

Management of the sensitized pediatric renal transplant candidate

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