Logo image
Back
Manufacturing as biology: How T-cell processing shapes therapeutic outcomes
Journal article   Peer reviewed

Manufacturing as biology: How T-cell processing shapes therapeutic outcomes

Nikolai Przybylski, Qinghe Zeng and Xiao Huang
Advances in Pharmacology, Forthcoming
2026
DOI: https://doi.org/10.1016/bs.apha.2026.05.005

Abstract

Cell quality Cell quantity Ex vivo stimulation T-cell manufacturing T-cell phenotype
T-cell therapies have transformed the treatment landscape for hematologic malignancies and show growing promise for solid tumors and non-oncologic diseases. Unlike conventional drugs, these living therapeutics are shaped not only by genetic engineering but also by the ex vivo manufacturing process itself, which functions as a powerful biological determinant of cell fate and function. Here, we present a framework that conceptualizes manufacturing as a form of biological programming that governs therapeutic outcomes through its effects on T-cell phenotype, fitness, and functional durability. We review how each major processing step, including isolation, selection, activation, transduction, expansion, and formulation, influences the balance between cell quantity and quality, the two principal determinants of clinical efficacy. Particular emphasis is placed on how extracellular cues encountered during manufacturing, such as physical properties of activation materials, stimulatory ligand presentation, cytokine and nutrient composition, and gene delivery method, shape transcriptional, epigenetic, and metabolic programs that define cell phenotypes directly linked to cell quantity and quality. Emerging strategies to deliberately steer T-cell differentiation toward persistence-associated phenotypes, enhance metabolic fitness, and reduce vein-to-vein time are highlighted as critical avenues for next-generation manufacturing. Additionally, reducing inconsistency and cost remain areas of strategic importance to expand availability. Collectively, this review underscores that optimizing T-cell therapy requires treating manufacturing not as a logistical necessity but as a controllable biological intervention. A mechanistic understanding of how processing decisions program cellular behavior will enable the rational design of more potent, durable, and scalable T-cell products for diverse clinical applications.

Metrics

1 Record Views

Details

Logo image