| Autor: |
Joshua A. Hill, Elizabeth M. Krantz, Kevin A. Hay, Sayan Dasgupta, Terry Stevens-Ayers, Rachel A. Bender Ignacio, Merav Bar, Joyce Maalouf, Sindhu Cherian, Xueyan Chen, Greg Pepper, Stanley R. Riddell, David G. Maloney, Michael J. Boeckh, Cameron J. Turtle |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Blood Advances, Vol 3, Iss 22, Pp 3590-3601 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2473-9529 |
| DOI: |
10.1182/bloodadvances.2019000717 |
| Popis: |
Abstract: The long-term effects of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy (CD19-CARTx) for B-cell malignancies on humoral immunity are unclear. We examined antiviral humoral immunity in 39 adults with B-cell malignancies who achieved durable complete remission without additional therapy for >6 months after CD19-CARTx. Despite CD19+ B-cell aplasia in all patients, the incidence of viral infections occurring >90 days post–CD19-CARTx was low (0.91 infections per person-year). Because long-lived plasma cells are CD19− and should not be direct targets of CD19-targeted chimeric antigen receptor T cells, we tested the hypothesis that humoral immunity was preserved after CD19-CARTx based on linear mixed-effects models of changes in serum total immunoglobulin G (IgG) concentration, measles IgG concentration, and the number of viruses or viral epitopes to which serum IgG was directed (the “antivirome”) using the novel VirScan assay. Samples were tested pre–CD19-CARTx and ∼1, 6, and 12 months post–CD19-CARTx. Although total IgG concentration was lower post–CD19-CARTx (mean change, −17.5%), measles IgG concentration was similar (mean change, 1.2%). Only 1 participant lost measles seroprotection post–CD19-CARTx but had undergone allogeneic hematopoietic cell transplantation before CD19-CARTx. The antivirome was also preserved, with mean absolute losses of 0.3 viruses and 6 viral epitopes detected between pre- and post–CD19-CARTx samples. Most participants gained IgG to ≥2 epitopes for ≥2 viruses, suggesting that humoral immunity to some viruses may be maintained or recover after successful CD19-CARTx. These findings may differ in children. Studies of immunoglobulin replacement and vaccination after CARTx are warranted. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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