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| Item Type: | Article |
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| Title: | Latent human herpesvirus 6 is reactivated in CAR T cells |
| Creators: |
Lareau, C.A.  ORCID: https://orcid.org/0000-0003-4179-4807, Yin, Y. ORCID: https://orcid.org/0000-0002-2220-005X, Maurer, K. ORCID: https://orcid.org/0000-0002-4160-181X, Sandor, K.D. ORCID: https://orcid.org/0000-0003-2892-4865, Daniel, B. ORCID: https://orcid.org/0000-0002-2410-8767, Yagnik, G., Peña, J. ORCID: https://orcid.org/0000-0002-9662-906X, Crawford, J.C. ORCID: https://orcid.org/0000-0003-4096-6048, Spanjaart, A.M. ORCID: https://orcid.org/0000-0003-0167-6021, Gutierrez, J.C., Haradhvala, N.J. ORCID: https://orcid.org/0000-0003-1113-3135, Riberdy, J.M., Abay, T. ORCID: https://orcid.org/0009-0009-0024-2732, Stickels, R.R. ORCID: https://orcid.org/0000-0003-4326-4084, Verboon, J.M., Liu, V. ORCID: https://orcid.org/0000-0002-6790-6603, Buquicchio, F.A., Wang, F. ORCID: https://orcid.org/0009-0000-8310-3088, Southard, J., Song, R., Li, W., Shrestha, A., Parida, L. ORCID: https://orcid.org/0000-0002-7872-5074, Getz, G. ORCID: https://orcid.org/0000-0002-0936-0753, Maus, M.V. ORCID: https://orcid.org/0000-0002-7578-0393, Li, S. ORCID: https://orcid.org/0000-0001-9106-6141, Moore, A., Roberts, Z.J., Ludwig, L.S. ORCID: https://orcid.org/0000-0002-2916-2164, Talleur, A.C. ORCID: https://orcid.org/0000-0002-6558-6706, Thomas, P.G. ORCID: https://orcid.org/0000-0001-7955-0256, Dehghani, H., Pertel, T., Kundaje, A. ORCID: https://orcid.org/0000-0003-3084-2287, Gottschalk, S. ORCID: https://orcid.org/0000-0003-3991-7468, Roth, T.L. ORCID: https://orcid.org/0000-0002-3970-9573, Kersten, M.J. ORCID: https://orcid.org/0000-0002-8904-3802, Wu, C.J. ORCID: https://orcid.org/0000-0002-3348-5054, Majzner, R.G. ORCID: https://orcid.org/0000-0001-6969-8011 and Satpathy, A.T. ORCID: https://orcid.org/0000-0002-5167-537X
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| Abstract: | Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6). Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4(+) T cells. Using single-cell sequencing, we identify a rare population of HHV-6 'super-expressors' (about 1 in 300-10,000 cells) that possess high viral transcriptional activity, among research-grade allogeneic chimeric antigen receptor (CAR) T cells. By analysing single-cell sequencing data from patients receiving cell therapy products that are approved by the US Food and Drug Administration or are in clinical studies, we identify the presence of HHV-6-super-expressor CAR T cells in patients in vivo. Together, the findings of our study demonstrate the utility of comprehensive genomics analyses in implicating cell therapy products as a potential source contributing to the lytic HHV-6 infection that has been reported in clinical trials and may influence the design and production of autologous and allogeneic cell therapies. |
| Keywords: | Viral DNA, Human Herpesvirus 6, Roseolovirus Infections, T-Lymphocytes, Viral Load |
| Source: | Nature |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Volume: | 623 |
| Page Range: | 608-615 |
| Date: | 16 November 2023 |
| Additional Information: | Copyright © The Author(s), under exclusive licence to Springer Nature Limited 2023 |
| Official Publication: | https://doi.org/10.1038/s41586-023-06704-2 |
| External Fulltext: | View full text on external repository or document server |
| PubMed: | View item in PubMed |
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