Host immune responses play a major role in clearance of viral infections from the body, and may limit long-term expression and clinical efficacy of viral vectors. Methods to prevent these immune responses may also increase the risk for infections, recombination with wild type virus and affect biodistribution, persistence, shedding and transmission. The study described in this report was initiated to assess possible environmental risks associated with the use of immune modulation in combination with
gene therapy and set up as a literature study, by performing
PubMed searches for certain keywords, by interviewing
experts and by attending selected meetings. Lack of
availability of clinical data combining gene therapy and
immune modulation and limited animal data warranted additional exploration of relevant non-gene therapy studies from closely related fields such as stem cell and organ transplantation, and vaccination studies with live attenuated vaccines.
Finally, we propose the use of a checklist to assess
current environmental risks in the use of immune modulation
during gene therapy. This report is expected to
provide guidance to risk assessors and regulatory officers
as well as to applicants for a gene therapy licence.