The recently concluded American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting (New Orleans, May 13-17) showcased ongoing innovations and clinical advances that are helping to realize the full potential of precision genetic and cellular medicines. The FINN Health Strategic Scientific Communications (SSC) team took a deep dive into the more than 2,000 abstracts included in this year’s meeting to identify major trends as well as exciting data sets that demonstrate important progress toward addressing historic challenges that have limited the use and accessibility of these potentially transformative therapeutic modalities. 

Major Trends

Our trend analysis identified five main takeaways from this year’s ASGCT abstracts:

• Continued maturation and clinical translation of adeno-associated virus (AAV)-based therapies.
• Advancement of CRISPR/RNA-editing platforms into clinical testing.
• Growing emphasis on non-viral delivery and systemic administration, with particular emphasis on improving tissue-specific targeting and delivery.
• Increased focus on understanding and modulating the immune and epigenetic environment for durable efficacy of gene and cell therapies.
• Greater recognition that improved scalability, efficiency, and quality of manufacturing processes are essential for reducing the time and cost of producing cell and gene therapies and making these potentially life-saving treatments available to more patients.

These two abstracts provide broad perspectives on the evolving gene therapy landscape:

• Abstract 1852 - Bemanalizadeh B and Mansouri V. Over a Decade of Gene Therapy Trials: Evolution from 2010 to 2025
• Abstract 1384 - Naresh NU. As new gene and cell therapies emerge from academia, we must RISE to the opportunity. 

Additionally, we call your attention to a recent New York Times article describing a rapid, collaborative approach to developing the world’s first, personalized gene editing therapy. The seeming success of this endeavor in the treatment of an infant with an ultra-rare disease reminds us that, beyond science and technology, there are real people in desperate need of innovative therapies. Here’s to everyone working diligently to realize the potential of gene and cell therapies.

Excitement on the Horizon

Beyond the major trends, which may not be surprising to those who follow the field closely, our team was excited by a variety of data sets that highlight important progress toward overcoming historic gene and cell therapy challenges. 

Read on to see what most intrigued our SSC team members.

Earlier in my scientific communications career, I worked at a company developing AAV and non-viral gene therapies. In the more than 20 years since that experience, immune responses to AAV have posed a challenge to initial dosing of patients with pre-existing anti-AAV antibodies resulting from exposure to naturally occurring AAV and to re-dosing patients treated with AAV-based gene therapies. Multiple abstracts describe a variety of innovative approaches to overcoming this challenge, including development of novel AAV vectors that show less immune cross-reactivity with the vectors used in approved and investigational AAV-based therapies and ways to modulate the immune response at the time of dosing to reduce the development of neutralizing antibodies against AAV. Examples of these abstracts include:

• Abstract 290 – Giovannone N. – Successful AAV vector re-administration via two distinct B cell immunomodulation strategies in non-human primates:
  • Demonstrates the potential of CD40 antagonist mAb or a CD20/CD3 bispecific antibody to prevent development of neutralizing antibodies (nAbs) against AAV

• Abstract 293 – Boehler J et al. – Potential for AAV-SLB101-mediated gene transfer treatment in the context of natural seropositivity and after an AAVrh74 treatment:
  • Demonstrates the potential of vector engineering to generate novel vectors that have low immunologic cross reactivity with pre-existing or treatment-induced nAbs

• Abstract 295 – Kuipa M et al. – AAV-vectored PD-L1 Co-Expression as a Strategy to Enhance AAV-Delivered bNAb Efficacy:
  • Suggests that co-expression of PD-L1 at site of AAV-based therapy administration can reduce host immune responses 
    
    
• Abstract 1245 – Henry B et al. – Pre-Existing Immunity to Adeno-Associated Virus: A Global Meta-Analysis of Anti-AAV Neutralizing Antibodies in 9,887 Patients: 
  • Informs our understanding of rates of pre-existing AAV immunity across 28 countries
    
    
• Abstract 1980 – Chang C et al. – Short-Term Repeat Dosing of KJ103 (Ricefidase) Enables Sustained IgG Reduction for Enhanced AAV Gene Therapy:
  • Phase 2 data support the use of a novel IgG-degrading enzyme as a strategy for reducing nAb titers due to pre-existing immunity or prior AAV-based therapy

Despite the success of chimeric antigen receptor (CAR) T cells for the treatment of certain blood cancers, targeting solid tumors has been a major challenge for immunotherapies. Due to several obstacles, including tumor heterogeneity, T cell exhaustion, lack of pan-cellular targets for solid tumors, and other tumor-induced immune evasion strategies, solid tumors have ultimately eluded CAR T therapies. Multiple abstracts at ASGCT describe novel engineered immune effector cells for solid tumors are being developed to overcome these issues. Although early in their development, these different approaches highlight the potential of new engineered cell types to target and treat solid tumors, a significant barrier in cancer treatment. These exciting new technologies are covered in these selected abstracts: 

• Abstract 441 – Horovitz-Fried M et al. – T cell engineering using V(D)J recombination allows tumor growth inhibition in mice:
  • Suggests this novel immunotherapy approach known as VDJ targeting produces potent naïve T cells that may be transplanted in lower numbers and have increased persistence compared to T cells engineered with state-of-the-art technologies
    
    
• Abstract 442 – Hanina S et al. – Sensitive HLA-independent T cell Receptors Overcome Tumor Antigen Heterogeneity in Solid Tumors:
  • Positions CD70 as a pan-cancer target that may be targeted by a more sensitive immunotherapy such as CD70 HLA-independent T cells (HIT)
    
    
• Abstract 445 – Chaudhry K et al. – Multimodal T cell immunotherapy CAR-TA (B7-H3 CAR and PRAME Tumor Antigen cells) for pediatric brain and solid tumor patients:
  • Novel T-cell therapy (CAR-TA) addresses multiple tumor immune evasion strategies for the treatment of children with relapsed/refractory solid tumors
    
    
• Abstract 446 – Pan Y et al. – Allogeneic GPC3 CAR-iNKT cells show robust anti-tumor activity in hepatocellular carcinoma mouse models:
  • Allogeneic CAR-invariant natural killer T (iNKT) cells demonstrated exceptional anti-liver cancer potency in mice

As many of the abstracts in this meeting discuss, gene therapy has been hampered by the absence of vectors for genetic modification that have high specificity for  cell types of interest. AAV shows tropism for the liver that can defeat attempts to efficiently and effectively transduce cells in other organs that are sites of human disease. Intense development and creativity is being utilized to find alternatives to viral vectors and to modifications of capsids that allow detargeting of the liver and targeting of cells of interest for transduction that may allow gene therapy of a wide variety of congenital and acquired diseases. One of the major advances described is the use of AI and machine learning to identify key conjugations with capsid regions that provide the desired cellular specificity. Examples of these abstracts include:

• Abstract 162 – Berguig G et al. – Computationally Designed Miniproteins Enable Tissue-Specific Oligonucleotide Delivery Through Cell Surface Receptor-Targeting:
  • A bioengineering feat creating miniproteins that are machine designed and bind to receptors, like TfR1, for the translocation of therapeutic oligonucleotides to muscle, liver kidney and CNS

• Abstract 410 – Meggersee R et al. – Position-Specific Impact of RGD Motif in AAV Capsid Variants on Muscle Tissue Targeting and Integrin Binding Affinity:
  • Focusing on monogenic diseases, synthesized GCap family vectors combining RGD tissue targeting peptides in exposed capsid loops that demonstrate 10 to 1000-fold improvements in cardiac and skeletal muscle transduction in non-human primates (NHPs)

• Abstract 413 – Cramer M et al. – A Novel Neuromuscular AAV Capsid Combines Efficient Systemic Muscle and CNS Delivery with Liver Detargeting in NHP:
  • Using an AI-driven design platform, the authors engineered a liver-detargeted neuromuscular AAV capsid and validated its tropism in adult NHPs

• Abstract 1402 – Liu H et al. – Rational Design of AAV9 Capsids for Targeted Delivery to Muscle and Heart and Detargeting of the Liver:
  • Combining functional motifs for detargeting the liver while targeting muscle, AAV9-GAST-MyoAAV delivered its RNA payload with a 61-fold increase in mRNA expression in the heart, 34-fold in the quadriceps, and a 25-fold decrease in liver in adult mice

• Abstract 1403 – Lee B et al. – AI-guided Vector Engineering for Enhanced ALS Therapy:
  • Using AI to identify viral motifs of interest, authors identified 7-mer amino acids whose conjugation with AAV improve blood-brain barrier penetration and CNS delivery, and successfully transformed motor neurons with the hSTMN2 gene and showed improved axon regeneration and motor function

Despite the advances made in gene therapies, with documented successes in the treatment of a number of different conditions, commercial viability remains a considerable hurdle. Often this takes the form of a singular up-front payment. In many markets, these therapies are all but unavailable due to costs, and in others, availability is limited. While the science behind gene therapies is an exciting prospect, these treatments mean nothing if they are inaccessible. Multiple abstracts at ASGCT have outlined various novel approaches to limiting these costs, notably through improving production efficiencies and by shifting focus to “off-the-shelf” treatments that would allow for notably improved affordability. 

As the landscape of advanced therapeutics continues to evolve, pivotal Phase 2 and 3 trials provide critical insights into the safety and efficacy of next-generation treatments across a diverse range of complex diseases. From groundbreaking gene therapies for Duchenne muscular dystrophy to novel stem cell–based approaches for ovarian cancer, Stargardt disease, and Crohn’s-related perianal fistulas, these studies reflect the rapid innovation driving personalized and regenerative medicine. This section delves into these pivotal trials, underscoring how targeted therapies are reshaping the future of treatment.

• Abstract 8 – Galanis E et al. – Phase I/II trial of adipose tissue derived mesenchymal stem cell delivery of a measles virus strain engineered to express the sodium iodine symporter (MV-NIS) in ovarian cancer patients:
  • Demonstrates the potential of cell-based virus delivery. Phase 2 trial of stem cell–based delivery of engineered measles virus showed promising safety, survival benefit, and immune activation in heavily pretreated recurrent ovarian cancer patients.
    
    
• Abstract 476 – Milano F et al. – Dilanubicel improves single cord blood transplantation: updated results with a larger cohort:
  • Highlights the benefits of dilanubicel, an off-the-shelf, non-HLA-matched cell therapy. An easily scalable and accessible therapy, it safely enhances single cord blood transplant by supporting early recovery, reducing relapse, and eliminating the need for a second CB unit without increasing Graft versus Host Disease (GVHD) risk.
    
    
• Abstract 584 – Mahajan V et al. – Human retinal cell delivery of a bioengineered, synthetic protein sensitive to multiple wavelengths of light in patients with Stargardt disease:
  • Provides an update on intravitreal MCO-010, a novel optogenetic therapy. It was found to be safe and showed encouraging vision improvement in patients with severe Stargardt disease, supporting further clinical investigation.

• Abstract 355 – Mendell J et al. – Long-term functional outcomes and safety following delandistrogene moxeparvovec treatment in DMD: EMBARK 2-year results:
  • Delandistrogene moxeparvovec, an rAAVrh74 vector-based gene therapy, demonstrated significant and durable functional benefits over two years in ambulatory boys with Duchenne muscular dystrophy, with a favorable safety profile
    
    
• Abstract 438 – Laugel V et al. – GNT0004, Genethon's AAV-based gene therapy for Duchenne muscular dystrophy: long-term follow-up of ambulatory boys enrolled in the dose-escalation phase of GNT-016-MDYF:
  • GNT0004 gene therapy showed promising safety and clinical benefits in boys with Duchenne muscular dystrophy, with sustained creatine kinase (CK) reduction and functional improvement, supporting its advancement to pivotal trials