See article, p. 1645.

The use of genetically engineered adoptive cell therapies (ACT) involving retroviral or lentiviral transduction of patient T cells with DNA encoding a chimeric antigen receptor or a T-cell receptor (TCR) specific to a cancer-associated antigen has yielded great benefits for the treatment of several malignancies; however, relapse can occur. Extending preclinical findings that expression of transgenic TCRs by circulating T cells diminishes rapidly after reinfusion and that the commonly used murine stem-cell virus (MSCV) is subject to DNA methylation–based epigenetic silencing, Nowicki and colleagues investigated the applicability of these observations in patients. In 16 patients treated with TCR ACT, although the engineered T cells retained the transgenic DNA encoding the TCR, RNA- and protein-level expression of the transgene was markedly reduced by 70 days following infusion. Patients with the lowest expression of the transgene exhibited substantially increased levels of CpG methylation at the MSCV 5′...

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