Lee Kang-Zheng, Nguyen Tan Dai, Liu Dan
Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, Singapore, 138668, Singapore.
J Transl Med. 2025 Aug 12;23(1):899. doi: 10.1186/s12967-025-06836-1.
Viral transduction is a critical step in the manufacturing of genetically modified T cells for immunotherapies, yet conventional transduction methods suffer from low to medium efficiency, high vector consumption, and limited scalability.
To address these challenges, we introduce the Transduction Boosting Device (TransB), an innovative, automated, and closed-system platform designed to enable efficient and scalable gene delivery and overcome the limitations of conventional transduction methods. TransB improves cell-virus interactions by facilitating proximity between target cells and viral vectors.
TransB demonstrated up to 1-fold decrease in processing time, 3-fold reduction in viral vector consumption, and 0.7-fold increase in transduction efficiency compared to 24-well plate method for donor T cell transduction in studies evaluating its impact on transduction process. Comparison studies transducing T cells from three different donors with Lenti-GFP vectors showed that TransB achieved an average 0.5-fold improvement in transduction efficiencies while maintaining comparable post-transduction cell recovery, viability, growth, and phenotype compared to 24-well plate. Furthermore, TransB delivered consistent performance across two different input cell numbers demonstrating scalability of the process.
These findings suggest that TransB could significantly shorten the transduction time, reduce the transduction cost and improve the transduction efficiency for manufacturing genetically modified T cell therapies. It shows strong potential as a robust, efficient, and scalable platform to enhance T cell therapy manufacturing and help overcome current manufacturing challenges in the field.
病毒转导是用于免疫治疗的基因改造T细胞制造过程中的关键步骤，但传统的转导方法存在效率低至中等、载体消耗高以及可扩展性有限等问题。
为应对这些挑战，我们引入了转导增强装置（TransB），这是一个创新的、自动化的封闭系统平台，旨在实现高效且可扩展的基因递送，并克服传统转导方法的局限性。TransB通过促进靶细胞与病毒载体之间的接近度来改善细胞-病毒相互作用。
在评估其对转导过程影响的研究中，与24孔板法相比，TransB在供体T细胞转导中处理时间最多减少1倍，病毒载体消耗减少3倍，转导效率提高0.7倍。用慢病毒绿色荧光蛋白（Lenti-GFP）载体转导来自三个不同供体的T细胞的比较研究表明，与24孔板相比，TransB在转导效率上平均提高了0.5倍，同时在转导后细胞恢复、活力、生长和表型方面保持相当。此外，TransB在两种不同的输入细胞数量下都表现出一致的性能，证明了该过程的可扩展性。
这些发现表明，TransB可以显著缩短转导时间，降低转导成本，并提高基因改造T细胞疗法制造的转导效率。它显示出作为一个强大、高效且可扩展的平台的巨大潜力，以增强T细胞疗法制造并帮助克服该领域当前的制造挑战。
