Karthikeyan Devaraju, Senior Scientist at Cerba Research provided his thoughts on the top takeaways from the meeting.
2025’s ESGCT conference highlighted several transformative trends in the Cell & Gene Therapy (CGT) space, signaling a dynamic future for clinical development. One of the most exciting areas is the rise of in vivo CAR-T therapies, which aim to generate CAR-T cells directly within patients. This approach is gaining momentum, with companies like Esobiotec, now part of AstraZeneca, and others, including Ensoma Therapeutics, leading the charge and planning new clinical trials. This in vivo approach is complemented by innovations in delivery technology, manufacturing, and access to therapy. These innovations could significantly streamline manufacturing and distribution and improve access for many more patients.
Another major theme was the combination of oncolytic therapies with CAR/TCR-T approaches to enhance targeting of solid tumors—a critical challenge in oncology. The industry is also moving toward off-the-shelf CAR therapies, reducing reliance on patient-specific manufacturing. Techniques like epitope engineering are being widely adopted to boost CAR efficiency. In addition, autoimmune applications of CAR-T cells are advancing rapidly, with new data from Cabaletta Bio showing that preconditioning or lymphodepletion may no longer be necessary. While lentiviral vectors remain the backbone of CAR/TCR development, the future could see a shift toward mRNA-based approaches, non-viral vectors, and virus-like particles (VLPs).
In genome editing, in vivo strategies using LNPs and VLPs are entering clinical trials, particularly for large populations with conditions like PCSK9-related dyslipidemia. AAV-mediated delivery is also gaining traction with novel genome editing nucleases and variants in various stages for clinical translation. A compelling case study from UPenn demonstrated how personalized genome editing in vivo can treat ultra-rare diseases, a concept that could redefine precision medicine. The study also highlighted the leveraging of unique strengths of different institutes/parties coming together for delivering the therapy. Beyond CRISPR-Cas9, companies are exploring novel technologies such as RNA writers (Tessera Therapeutics) derived from retrotransposons, offering promising alternatives for future therapies.
Finally, gene therapy continues to rely heavily on AAV-mediated delivery, but innovation is accelerating with AI-designed capsids that promise improved targeting and efficiency. Reports from multiple players showed advancement, safety, and efficacy of AAV-based therapy. Another key highlight was stem cell derived transplants in Parkinson’s disease presented by Lorenz Studer from MSKC, New York that showing that stem cell derived therapies are a reality. These developments underscore a clear trend: the CGT field is evolving toward more precise, scalable, and patient-friendly solutions, paving the way for breakthroughs in oncology, rare diseases, and beyond.
ESGCT 2025 solidified the shift from “proof-of-concept” to scalable, precision-driven therapeutics. Cerba Research’s depth in cell and vector analytics, immunogenicity/ immune monitoring, multiomics and IND / IVDR dossier supports us as a strategic partner in accelerating these innovations into the clinic.
