A new study examining the long-term safety of gene therapies used in T cell treatments for HIV-1 infection and cancer has found reassuring results, though some risks remain. The study analysed safety data from 783 patients across 38 clinical trials, totalling over 2,200 patient-years of observation. These trials utilised integrating gammaretroviral and lentiviral vectors to deliver engineered receptors to target disease.
While the risks of gene therapy are still being evaluated, the study identified 18 patients (2.3%) who developed secondary malignancies after treatment. These cancers appeared with a median onset of 1.94 years, ranging from as soon as 51 days to up to 14 years post-treatment. Tumour samples were analysed where possible, but no clear signs of harmful vector insertions were found. Notably, one T cell lymphoma was detected, though it did not show signs of being linked to vector integration.
Further analysis of vector integration sites in 176 patients revealed no pathological insertions associated with secondary malignancies. Some integrations were found near specific genes, including tumour suppressor genes, but these did not seem to result in malignancy. In some cases, the integration led to modest clonal expansion and sustained T cell persistence, which could be beneficial for treatment efficacy.
This comprehensive study suggests that while secondary malignancies are a concern, overall, engineered T cell therapies show promising safety outcomes, paving the way for their continued development and use in treating HIV-1 and cancer.
Helena Bradbury, EMJ
Reference
Jadlowsky JK et al. Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies. Nat Med. 2025; doi: 10.1038/s41591-024-03478-6.
