Hamburg, the historic German port city known for its long-standing media presence and musical heritage, served as the venue for the European Society of Gene & Cell Therapy (ESGCT) conference from October 27 to 30, 2026. The event brought together researchers and clinicians to address critical themes including patient safety, the expansion of access to gene therapies, and the ongoing quest for an HIV vaccine.
During the opening plenary session, Dimitrios Mougiakakos presented findings on CAR T therapy for lupus. While noting progress in the field, he highlighted that lower risk does not equate to zero risk, citing patient deaths as a concern. Mougiakakos suggested that rapid production of CAR T cells could be a contributing factor and advocated for a more measured "Volkswagen approach" rather than a high-speed "Ferrari approach" to ensure safety.
Giuliana Ferrari, an Italian professor, discussed her team's work on beta-thalassemia, a condition characterized by over 400 different globin gene mutations. She reported on the ex vivo TIGET-BTHAL Phase I/II trial, which began in 2015. Results showed that while some patients had to restart blood transfusions, others remained transfusion-independent after nine years with respectable hemoglobin levels. To improve accessibility and affordability, Ferrari's team is launching a new Phase IIb academic trial, Bthal FT007-01, which has already enrolled its first two patients. This initiative features optimized manufacturing protocols, including a reduced cell culture and gene transduction time of 40 hours, down from the previous 60 hours, alongside changes to the conditioning regimen.
Bill Schief, who holds positions at Scripps Research Institute and as vice president of protein design at Moderna, addressed the urgent need for an HIV vaccine. Despite global efforts, more than 40 million people live with HIV, with over 20 percent lacking access to antiretroviral therapy. With 1.2 million new infections and 570,000 deaths annually, Schief emphasized that declining research funding makes a vaccine essential. His team is designing vaccines to guide the immune system toward broadly neutralizing antibodies (bnAbs) targeting vulnerable regions of the HIV envelope protein.
Schief outlined a complex strategy involving priming, shepherding, and polishing immunogens to induce multiple classes of bnAbs and long-lived plasma cells. Recent progress includes promising Phase I results reported in 2025 in Science, involving the IAVI G002 trial in the U.S. and the IAVI G003 trial in Rwanda and South Africa. Additionally, earlier this year, Schief's colleagues published findings in Nature demonstrating that germline-targeting vaccines can induce pre-specific bnAbs in non-human primates.
Michel Sadelain provided an overview of CAR T therapy's potential in oncology and other fields. He noted that survival duration for certain cancers has quadrupled from approximately six months to over 25 months, driven by two primary molecular designs. While promising data exists for rheumatology and preliminary results for neurology, progress against solid tumors lags behind hematological malignancies. Sadelain identified five key challenges: increasing T cell persistence, potency, and sensitivity, preventing toxicity, and identifying new targets.
To address these issues, Sadelain's team explored modulating signaling strength. In 2025, they demonstrated that switching from three ITAMs to a single ITAM created a strong effector function with greater persistence. This "1XX" signaling module was tested in B-cell lymphoma, yielding excellent responses with doses as low as 25 million cells, significantly less than the standard 100-400 million. Furthermore, the team utilized CRISPR to develop an HLA-independent T cell (HIT) receptor that is at least 10-fold more sensitive, with current characterization ongoing in solid tumor models such as renal cell carcinoma.