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

项目摘要/摘要 儿科基因治疗和医学伦理工作组(PGTME)--设在纽约大学格罗斯曼学校 医学部医学伦理部-计划在华盛顿特区举办为期一天的混合动力会议。 5月中旬，题为“基因治疗研究中针对病毒载体的抗体：寻求最佳实践” 赞助商政策和沟通。我们正在研究这一主题，以寻求可能的政策解决方案 针对基因治疗中使用的病毒载体的抗体(AB)检测的标准和沟通 (GT)研究。2021年，PGTME就这一主题举行了两次听证会和一次闭门会议。 这些会议的与会者提出了一些潜在的教育和/或结构性干预措施； 然而，关于哪些是可行和有效的，仍然存在疑问。PGTME正在召集一场多元化的 专家组将在此期间探讨可能的政策建议和沟通标准化 会议。 基因治疗(GT)干预目前不能被逆转或“关闭”，如果它们对 收件人。此外，通过病毒载体注射GTS会导致免疫后遗症 排除接受者参与未来的GT临床试验。因此，目前这些研究中的研究对象 只能接收一个可能改变生活的候选GT。考虑到关于GT的这组独特的事实 研究，重要的是患者和/或代孕决策者最好地了解 参与GT临床试验的潜在风险和好处，以及此类试验的影响 在时间、费用、努力和机会成本方面的参与。虽然有许多道德问题 围绕GT临床试验，拟议的会议只关注两个。首先，患者和/或护理者 目前正在进行或正在进行GT临床试验的患有罕见疾病的个人 预期经常从赞助商和其他实体收到关于抗体的不一致的信息 作为筛选GT临床试验潜在参与者资格的一部分而进行的水平测试。 其次，这些患者和/或照顾者往往没有得到适当或一致的 来自临床医生或试验赞助商的关于参与的免疫原性影响的沟通 GT研究。 我们完全期待这次会议的与会者之间的小组会议和其他非正式互动 会议将有助于推进实践和政策，以改善GT试验赞助商的信息传递 和临床医生了解抗体水平检测的用途，并将为旨在 更道德、更有效的GT临床试验。

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.