Key Themes From the 2021 ASGCT Meeting

The 24th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), May 12-15, 2021, showcased many innovations and new research in improving gene and cell therapy techniques and treatments. One study presented by Avamab Pharma, prompted by the COVID-19 pandemic, sought to improve monoclonal antibody (mAb) therapy as a strategy for passive immunization in older adults contraindicated for mRNA vaccines by using patients as a “bioreactor” to produce neutralizing mAbs in vivo via vectored immunoprophylaxis (VIP).

Investigators vectorized 3 mAbs (31C2, 15A7, and CR3022) that bind the SARS-CoV-2 spike protein and evaluated their expression and safety in mice and lambs. The 31C2 mAb had the strongest, dose-dependent expression, with a peak average human immunoglobulin G (hIgG) plasma serum concentration of 175.1 ug/mL and an average of 276.5 ug/mL hIgG in bronchoalveolar lavage fluid in mice. No signs of toxicity were seen in mice or lambs.

GeneTherapyLive spoke with Brad Thompson, PhD, chief executive officer, Avamab Pharma, to learn more about the company’s research and how the pandemic has affected all facets of research. He also discussed some themes he observed during the ASGCT meeting, including the pandemic’s silver lining of familiarizing the public with the use of gene therapy.

GeneTherapyLive: Were there any strong themes you noticed at this year’s meeting?

Brad Thompson, PhD: There were 3 or 4 underlying themes that came out of the meeting. The first was how COVID-19 has actually normalized gene therapy to the public, and, more pertinent to the gene therapy community, to investors. A lot of people don’t realize that the mRNA vaccines from Moderna and Pfizer are an example of gene therapy. People don’t like to talk about investors, and this was an academic conference, but it’s become increasingly commercial as more investments are made in the area. It’s broadened from specialist investors due to COVID-19.

Another thing that came out of the meeting is that people are going beyond “traditional” gene therapy, of correcting genetic defects in patients like cystic fibrosis, and things like that, and are looking at more novel applications. They're up- and down-regulating genes, investigating mRNA, genes themselves, and mRNA binding proteins. The field has broadened out rather dramatically along with the ways that people are trying to use gene therapy. There were whole sessions this year on types of applications in gene therapy that didn’t exist last year.

The third underlying theme was that people are starting to look closely at some of the safety and toxicology issues that are arising with gene and cell therapies. Everyone in the field knows there’s no such thing as “no tox.” I’ve been doing tox studies with gene therapy for over 2 decades and the FDA has been focused on toxicology since the start, but real attention in that area wasn’t evident at the meeting until this year. Anywhere that a virus goes, you have to worry about toxicology, mainly in the liver, but now we’re seeing cardiovascular toxicity with COVID vaccines, and people are also worried about neurotropic toxicity. You also have to worry about kidney toxicity. All this is pretty standard.

Was there anything surprising about the meeting?

There was nothing unexpected. There was certainly an increase in presentations with people doing gene therapy for infectious disease, by either juicing the immune system or amino prophylaxis. There was a ton of data, from presentations and plenaries on that. Last year, there was absolutely nothing on that.

There was still a lot of focus on rare diseases, which has been the underlying theme of gene therapy from the start. But we're also starting to see people talk about treating diseases that aren't rare, which is good. When we started setting up our gene therapy companies 4 or 5 years ago, we consciously chose not to do rare diseases.

Transcript edited for clarity.

REFERENCE

Rghei AD, van Lieshout LP, MCLeod B, et al. Vectorized SARS-CoV-2 human IgG Expression in mice and ovine animal models is feasible and well tolerated. Presented at: 2021 American Society of Gene & Cell Therapy Annual Meeting; May 12-15, 2021. Abstract 234.