#BIOSPAIN2026 | Abstract – Accelerating Cell & Gene Therapy Impact through analytical excellence

Cell and gene therapies (CGT) have reshaped modern biomedical innovation, offering curative potential for diseases once considered untreatable. Immune checkpoint inhibitors, 4^th generation CAR T‑cells, TCR therapies, and more have all attracted sustained investment and global scientific attention. Yet despite this momentum, the translation of CGT innovation into reliable, scalable, and safe therapies remains one of the most complex challenges in life sciences. 

The development of cell therapies is fundamentally different from that of traditional biologics. These therapies are dynamic, living products whose function depends on factors such as phenotype, metabolic fitness, activation state, persistence, and their interactions with the surrounding biological environment. As a result, comprehensive characterization is essential to understand and ensure their quality, safety, and performance.

This is where Agilent’s cell and molecular analysis portfolio plays a decisive role, providing multi-modal, high-resolution tools that enable developers to deeply characterize engineered immune cells across discovery, process development, and manufacturing.

One of the most pressing challenges in CGT, particularly in CAR T cell therapies, is response durability, especially in solid tumors. Unlike hematological malignancies, solid tumors present hurdles such as antigen heterogeneity, immunosuppressive cell populations, and metabolic constraints that impair immune cell persistence and killing efficacy. Overcoming these obstacles requires iterative genetic engineering supported by multimodal analytical workflows. Agilent’s platforms enable developers to combine flow cytometry, metabolic analysis, imaging, and functional assays to build a holistic understanding of immune cell behavior.

Understanding and optimizing metabolic fitness in the context of cell therapies is essential. Agilent’s Seahorse XF analyzer allows developers to quantify mitochondrial respiration, glycolysis, ATP production, and spare respiratory capacity in real time. These parameters are increasingly evaluated as potential quality attributes (CQAs) associated with cell function and phenotype in research. By integrating metabolic profiling early in development, researchers can gain insights into cellular function and identify opportunities to optimize engineered cell characteristics and their interactions with complex biological environments.

Another major barrier is toxicity management, including cytokine release syndrome (CRS), neurotoxicity, and on‑target/off‑tumor effects. These risks underscore the need for precise immunophenotyping and cytokine profiling during preclinical studies. Agilent’s NovoCyte flow cytometers support multiplex analysis of cell activation markers, inhibitory receptors, differentiation states, and cytokine secretion. Multiplex bead‑based assays further enable simultaneous quantification of inflammatory cytokines, providing a detailed view of immune cell activation and helping developers better understand and monitor potential toxicity-related responses during development.

This analytical depth provides a more comprehensive understanding of product attributes, supporting robust characterization and informed research decisions.

A cornerstone of CGT translation is the development of robust functional potency assays. Traditional endpoint assays often fail to capture the dynamic nature of immune cell mediated killing. Agilent’s xCELLigence real‑time cell analysis platform provides continuous, label‑free measurement of cytotoxicity, capable of revealing kinetic profiles of immune cell engagement, killing efficiency, and serial killing capacity over days or even weeks. This information can be vital in assessing response durability. These real‑time assays offer richer insights than static measurements and can develop into validated QC release assays, supporting regulatory compliance and batch‑to‑batch consistency.

Imaging‑based approaches further strengthen functional characterization. Automated live‑cell imaging systems quantify proliferation, activation, clustering, and cytotoxicity with high temporal resolution. Confocal imaging and 3D assay formats allow developers to study immune cell engagement within physiologically relevant microenvironments, bridging the gap between invitro models and real-world applications. These tools help developers understand how engineered cells behave in complex tumor structures, supporting the understanding of cellular behavior.

Finally, as we begin to see a shift to mRNA-based cell and gene therapies, it’s important to ensure product quality via rigorous QC at every step as RNA is highly prone to degradation and susceptible to impurities. From plasmid or PCR template, through to transcription, polyA tailing and final product formulation, critical quality attributes (CQAs) focus on mRNA integrity, size, purity, and polyA tail characteristics. Automated capillary electrophoresis such as Agilent’s Fragment Analyzer enables the sensitive assessment of these attributes, supporting reliable, high-quality mRNA production for therapeutic applications.

Scientific challenges aside, CGT development requires new commercialization and manufacturing models. Autologous therapies demand precise coordination across collection, engineering, expansion, and delivery. Allogeneic platforms promise scalability but require rigorous analytical control to ensure consistency. Regulatory agencies emphasize early definition of CQAs and critical process parameters (CPPs), making analytical excellence a strategic necessity. Agilent’s cell and molecular analysis solutions support this need by enabling deep characterization of starting materials, engineered products, and final therapeutic batches.

Ultimately, the future of CGT depends on integrating scientific creativity with analytical discipline. Breakthrough therapies require more than engineering; they require precise measurement, functional validation, and deep biological insight. Agilent’s cell analysis and molecular technologies empower developers to meet these demands, enabling the field to move from promising prototypes to advanced research programs.

PR7005-2111

For Research Use Only. Not for use in diagnostic procedures.