The Vector
Editorial Team
Karen Bulaklak, PhD – Editor, The Vector
Jon Brudvig, PhD – Associate Editor, The Vector
Jessica Schneller, PhD – Junior Editor, The Vector
Inside This Issue
Leadership Message
Breaking Through
From Molecular Therapy
Society News
Career Center
Public Policy
Industry News
Leadership Message
Send Us Your Abstracts Through Feb. 3
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Hello ASGCT members,
Happy New Year! I hope you all enjoyed the holiday season and were able to relax and spend time with loved ones before heading into 2023. We’re gearing up for so many exciting events and opportunities this year and look forward to sharing them with you. First, though, I want to tell you why you should consider submitting an abstract, which you can do through Friday, Feb. 3.
If you’ve not previously submitted your research for presentation at the ASGCT Annual Meeting, please consider taking advantage of this exciting opportunity. Our abstract presentations, which include oral and poster sessions, serve as the “scientific backbone” of the meeting. If your abstract is accepted, you’ll be able to share your research in person with the largest international gathering of gene and cell therapy professionals. I must say, there is nothing like attending the Annual Meeting and discussing the latest findings in person, especially after two years of virtual meetings!
In addition to presenting your work and discussing with colleagues at the meeting, there are other benefits to abstract submission. You may be eligible for one of our awards for high-scoring research. If you’re an associate member of ASGCT, a first author and presenting the abstract, you can register to attend the meeting for free. Finally, if accepted, your research will get published in a supplement to Molecular Therapy, our flagship, high-impact journal.
When you’re ready to send us your work, please submit it here by Feb. 3. You’ll select one first choice and one second choice topic from this list that best describes your abstract. Remember that there will be NO abstract extension this year. We will be accepting late-breaking abstract submissions again beginning Feb. 13, but that deadline is not intended to be an extension of the general submission deadline. As always, we look forward to seeing your fantastic work during the meeting this spring!
Sincerely,
Isabelle Rivière, PhD
ASGCT Secretary
Breaking Through
Transient secretion of VEGF protein from transplanted hiPSC-CMs enhances engraftment and improves rat heart function post MI
Ai X, Yan B, Witman N, Gong Y, Yang L, Tan Y, Chen Y, Liu M, Lu T, Luo R, Wang H, Chien KR, Wang W, and Fu W
DOI: https://doi.org/10.1016/j.ymthe.2022.08.012
Summary by Karen Bulaklak, PhD
Heart failure (HF) is a leading cause of morbidity, affecting over 60 million people worldwide. It is defined by impaired blood pumping capacity of the heart and is progressive in nature. Despite the high prevalence in the population, treatment options for severe cases are limited. Cell-based therapies have been pursued by researchers for their regenerative potential via stimulation of cardiac repair or engraftment within the host myocardium. Examples of such treatments are the use of skeletal muscle myoblasts, mesenchymal stem cells, and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Major hurdles for these treatments are poor viability and engraftment of the transplanted cells, which is thought to be impaired by the diseased microenvironment. To modify the microenvironment in HF, in vivo protein expression has also been utilized. One example is vascular endothelial growth factor (VEGF)-A expression, which been shown to promote angiogenesis, cardiomyocyte proliferation and survival, and ultimately functional outcomes. Although both strategies show promise, a recent report by Ai et al described a combinatorial approach to meet the need for HF treatments.
To combine the two strategies and enhance their efficacy, Ai and researchers used an approach involving transient overexpression of VEGF in iPSC-CMs via chemically modified mRNAs (modRNAs). These “iPSC-CMmodVEGF” would serve as delivery vehicles for VEGF and have the capacity to engraft into the myocardium. Extensive characterization of the iPSC-CMmodVEGF showed that these cells continually secreted and accumulated VEGF in the media over one week, which could stimulate angiogenesis in vitro. RNA sequencing and analysis of iPSC-CMmodVEGF revealed upregulation of genes associated with cardiac muscle contraction and cellular adhesion, which could promote cell proliferation and engraftment. When delivered into a rat model of myocardial infarction (MI), areas transplanted with iPSC-CMmodVEGF showed engraftment and remuscularization compared to a luciferase modRNA-treated iPSC-CM control. Fibrotic area and infarct size were reduced with iPSC-CMmodVEGF, and left ventricular (LV) wall thickness was greater compared to the untreated hearts. The group also reported continual angiogenesis in treated hearts over the course of the study. Finally, echocardiogram revealed a beneficial effect of the iPSC-CMmodVEGF on LV function that continued to improve compared to the control groups over time.
While the results are promising, the authors did note that further investigation is needed to improve integration of transplanted cells in the existing host myocardium and to understand the optimal maturity of the iPSC-CMs to avoid the possibility of arrhythmias. Nevertheless, similar combination approaches could be applied to other cell-based therapies and hopefully overcome common obstacles within the field.
From Molecular Therapy
Submit a nomination for the inaugural Best of Molecular Therapy Award
Nominate yourself or a colleague for this award by Feb. 28, 2023! The Best of Molecular Therapy Award, supported by Phil and Nancy Reilly, highlights the contributions of leading early-career authors to the Molecular Therapy family of journals.To learn more about the nomination criteria, please visit this section of our website.
Special issue call for papers: Biomanufacturing in gene and cell therapy
Submit to a special issue of Molecular Therapy—Methods and Clinical Development by May 31! The issue will be dedicated to all aspects of preclinical and clinical manufacturing of gene and cell therapy products. Learn more and submit today!
Latest MT issues: Check out the most recent issues of these Molecular Therapy family journals:
Society News
Register for Free ASGCT-FDA Immunogenicity Event Jan. 24-25
Join expert ASGCT members and FDA speakers as they discuss appropriate approaches to immunogenicity for clinicians, regulators, and developers. During Immune Responses to AAV Vectors, attendees will learn the latest on controlling immunogenicity during clinical development. Learn more and register on our website.
Shape the Future of the Society by Applying for a Committee
We're seeking committee members for the 2023-2024 program year, and we need your nominations by Jan. 31! If you've ever wanted to help develop Annual Meeting symposia or Insight Series events, hone your leadership skills, or meet more of your fellow members, this is your chance. If you are a current member renewed through 2023, you can submit your nomination here by Jan. 31.
Save on Annual Meeting Registration with Early-Bird Rates
Want to save on your registration for the 26th Annual Meeting? Register by Feb. 28 to receive the lowest rates! We've expanded the meeting to four full days this year, so register now to secure your spot at the largest gathering of gene and cell therapy professionals.
Career Center
Are you looking for a job in the field of gene and cell therapy? Check out the new ASGCT Career Center for great opportunities with industry, government, and academic organizations. Sign up to receive alerts for open jobs in your area.
If you're from a recruiting institution, advertise in the Featured Jobs section to target the 5,000+ audience of The Vector.
Featured Jobs
Public Policy
Jan. 15: Last Day to Apply for Congressional Policy Fellowship
The application window for the inaugural Congressional Policy Fellowship will close this Sunday, Jan. 15! In partnership with AAAS, we'll select one applicant for a one-year policy fellowship in legislative offices on Capitol Hill beginning in the fall of 2023. Fellows will provide high-quality, science-based, independent guidance to federal policy makers and elevate awareness of the Society among policymaking circles. Previous fellows describe how this opportunity helped shape their careers and created a lifelong network of contacts and mentors. Fellows must be an ASGCT member with a doctoral degree looking to learn more about the intersection of science and policy. A summary of application materials and FAQ are available, so apply today!
New Gene Therapy Approved for Bladder Cancer
Ferring Pharmaceuticals recently won U.S. approval of its gene therapy for a high-risk, non-muscle-invasive bladder cancer (NMIBC) that is not responsive to Bacillus Calmette-Guérin (BCG) immunotherapy. Adstiladrin (nadofaragene firadenovec) is a non-replicating adenoviral vector-based gene therapy that delivers genetic material to bladder cells to help produce cancer-fighting interferon. Adstiladrin was approved following positive results in a phase 3 trial, showing a complete response in just over half of the participants. Adstiladrin has faced various manufacturing challenges on the road to approval, and the product will not be commercially available until the second half of 2023 to allow for scale-up.
Following the approval ASGCT's president shared additional detail about bladder cancer and how this type of gene therapy works. This approval marks the seventh gene therapy approved for use in the U.S., more than doubling the number of approved products from the beginning of 2022.
Government Spending Package Includes Key Provisions for CGT
Just before the new year, Congress passed a spending package for the 2023 Fiscal Year (FY23), which runs through September 30, 2023. The package is known as an omnibus spending bill due to its inclusion of all appropriations bills and the large number of other bills and policies. ASGCT is encouraged that a number of Society-supported positions are included. A blog post with a full summary of relevant provisions is now available, but in preview the bill includes:
- Increased funding for the Food and Drug Administration (FDA), National Institutes of Health (NIH), and Advanced Research Projects Agency for Health (ARPA-H)
- Reforms to the accelerated approval pathway
- New requirements for clinical trial diversity plans
- New programs to boost and streamline CGT manufacturing, including for platform technologies and advanced manufacturing technologies
ASGCT will follow the implementation of these various policy riders as we settle into 2023, and will continue to engage with policymakers on the issues most important to the field and to our members.
Read Our Comments to FDA on Ethical Considerations for Pediatric Subjects
ASGCT submitted comments earlier this month to FDA on the draft guidance: Ethical Considerations for Clinical Investigations of Medical Products Involving Children. In the response, ASGCT supported the protection of human subjects in FDA-regulated clinical investigations through adherence to current clinical trial regulations and robust Institutional Review Board (IRB) processes and commended practices that ensure vigorous safeguards for children involved in clinical research.
Pediatric research principles, including the ethical questions addressed in the guidance, are of particular relevance for product sponsors, academic researchers, and interested patient groups currently engaged in bringing the next generation of current gene and cell therapy products to market given the pipeline’s focus on pediatric indications. The cell and gene therapy pipeline offers a unique opportunity to address pediatric diseases, many of which do not have available treatment options. In comments, ASGCT advocated for:
- Pediatric non-clinical data sources to be used when adult data is not available or otherwise unethical
- Additional safeguards around informed consent, including unique mechanisms of action, potentially durable treatment effect, uncertain oncogenic risk profile, and the ethics of control arms in rapidly degenerative diseases
- IRBs to consider the innate differences between CGT and small molecule products when offering guidance on pediatric risk-benefit considerations
The Society is committed to the safety and protection of pediatric and adult patients in clinical trials and will continue to engage on these issues as additional regulatory opportunities arise.