T Cell-Based HIV Gene Therapy Safe Over Long Term
No evidence of vector-induced cell immortalization, persistent clonal expansion
FRIDAY, May 4 (HealthDay News) -- T cell-based gene therapy for HIV seems safe, with no evidence of vector-induced cell immortalization more than a decade after treatment, according to a study published in the May 2 issue of Science Translational Medicine.
John Scholler, from the University of Pennsylvania Perelman School of Medicine in Philadelphia, and colleagues performed a follow-up of HIV-infected patients who had received gene therapy consisting of T cells engineered with CD4 linked to the CD3ζ signaling chain as part of three clinical trials at least eleven years earlier.
The researchers found that the engineered T cells were still detectable in 98 percent of samples, with no evidence of vector-induced immortalization. There was no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in transformation or growth control. The modified cells were stably engrafted, with a half-life of at least 16 years, and remained functional.
"Our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient-years of follow-up," Scholler and colleagues conclude. "Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors."
One author is employed by Celgene; another author disclosed working as an advisor and clinical investigator for biopharmaceutical companies.