Trivalent Virus-Specific T cell Biobank enables rapid treatment of sever viral infections in immuncompromised patients

Hematopoietic stem cell transplantation and solid organ transplantation cause significant immune deficiency, exposing patients to life-threatening infections. These viral opportunistic or reactivation infections are difficult to treat, leading to high morbidity, long hospital stay periods, and significant mortality. Some diseases are incurable due to the lack of conventional drugs` efficacy or resistant infections. Adoptive cell therapy specifically directed against pathogen target molecules is an emerging modality to reduce viral load and viral infection clinical manifestations. Recently, we established an “off-the-shelf” biobank with different batches of trivalent viral-specific T cells (VSTs). VSTs are simultaneously activated against AdV, BKV, CMV, or EBV immunogenic viral peptides. These biobank products and the overall platform established provide a rapidly available cellular therapy option for patients with clinically significant viral infections, even in the case of no available donor. To date, eleven clinical-grade VST batches have been manufactured from healthy donors, eight of them produced to target ADV, BKV, and CMV and three produced to target EBV. The products met regulatory specifications and retained viability, recovery, and antigen-specific activation after cryopreservation and thawing. Each production generated high numbers of activated cells, enabling sequential dosing without additional manufacturing. Twelve patients were treated under a compassionate protocol; seven of them received third-party products. Seven patients received sequential treatment in a dose-escalating manner and showed significant reduction of viral load. This “off-the-shelf” VSTs biobank platform transforms infectious disease therapy for immunocompromised patients into a scalable, rapidly accessible, and thus lifesaving approach.