Antibodies to Viral Vectors in Gene Therapy Research: Seeking Best Practices for Sponsor Policies and Communications

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Project Summary/Abstract The Pediatric Gene Therapy and Medical Ethics Working Group (PGTME)—housed in NYU Grossman School of Medicine’s Division of Medical Ethics—is planning to host a one-day hybrid conference in Washington D.C. in mid-May entitled, “Antibodies to Viral Vectors in Gene Therapy Research: Seeking Best Practices for Sponsor Policies and Communications.” We are researching this topic in pursuit of possible policy solutions addressing standards of and communication around antibody (AB) testing to viral vectors used in gene therapy (GT) research. In 2021, PGTME held two listening sessions and one closed-door meeting on this topic. Participants from these meetings raised a number of potential educational and/or structural interventions; however, there remain questions around which are feasible and effective. PGTME is convening a diverse group of experts to explore possible policy recommendations and communication standardization during this conference. Gene therapy (GT) interventions cannot currently be reversed or “turned off,” should they cause harm to the recipient. Furthermore, GTs administered by means of a viral vector result in immunologic sequelae which preclude recipients’ participation in future GT clinical trials. Thus, at present, research subjects in these studies are only able to receive one potentially life-altering candidate GT. Given this unique set of facts about GT research, it is essential that patients and/or surrogate decision-makers have the best possible understanding of the potential risks and benefits of participating in a GT clinical trial, as well as the implications of such trial participation in terms of time, expense, effort, and opportunity costs. While there are numerous ethical issues surrounding GT clinical trials, the proposed conference focuses on only two. First, patients and/or caregivers of individuals with rare diseases for which GT clinical trials are currently underway or are currently anticipated often receive inconsistent messaging from sponsors and other entities about the antibody level testing done as part of screening a potential participant for eligibility in a GT clinical trial. Secondly, these patients and/or caregivers often do not receive appropriate or consistent communication from clinicians or trial sponsors about immunogenic implications of participating in GT research. We fully anticipate that the panel sessions and other informal interactions between the participants of this conference will contribute to advancing practices and policies that improve messaging from GT trial sponsors and clinicians about antibody level testing utility and will set the basis for collaborative approaches aimed at more ethical and more efficient GT clinical trials.