Cell and gene therapy (CGT) aims at modifying the expression of a gene or the biological cell properties for therapeutic purposes. Corresponding products embrace cellular immunotherapies and other types of both autologous and allogeneic therapies for specific indications, including oncological and neurological as well as rare genetic disorders. Both types of therapies are highly complex. They require appropriately matched analytical development approaches to ensure a high level of consistency during production for safety.

The global cell and gene therapy market is expanding rapidly and, according to recently published market research results, is expected to more than triple within the next seven years from USD 1.46 billion in 2020 to USD 5.02 billion by 2028 at a CAGR of 17.0%. Developers face analytical challenges as regulators are seeking more detailed information and tighten their requirements. Strong, meaningful and efficient analytical solutions are needed throughout the development process in order to ensure the highest possible degree of product and process control and to meet the regulatory demands.

Mass spectrometry as a versatile analytical approach in CGT developments

As a high-resolution analytical method, mass spectrometry is a versatile tool routinely used for in-depth studies within the development of various biopharmaceuticals. Over the past years advances in analytical MS technology have reinforced its key role in ensuring a product’s quality and consistency. Based on two decades of experience in this sector Protagen Protein Services is your expert in applying mass spectrometry techniques to a broad range of biopharmaceuticals, including CGT. In the light of our profound expertise in MS application and data interpretation we offer mass spectrometry as a powerful tool for development and in the field of product- and process-related quality control, GMP, and release-related testing.

Deep understanding from structure to function

LC-MS is a state-of-the-art technique, with diverse methods for helping to understand the product from structure to function. In addition to initial and extended characterization, for example with regard to posttranslational modifications (PTMs), peptide mapping, and degradation studies, it also serves as a core technique to fulfill characterization demands when filing. We apply advanced analytical approaches for the development of cell and gene therapies including:

  • vector protein characterization and PTM analysis (correlations to infectivity),
  • LC-MS HCP profiling in vector production lots,
  • identification and quantification of gene-edited proteins in target cells and tissues,
  • quantitation and characterization of expression products in cells, pre-clinical and clinical samples.

In vivo analysis of critical quality attributes

Quantitative analysis of gene expression products in patients is vital for the evaluation and optimization of the cell and gene therapy platforms. In many cases, a substantial background of highly similar protein is already present in the tissue. MS-based analysis provides an accurate and sensitive method for quantifying and differentiating therapeutic expression from the background. Hence, it can be used to track the persistence of therapeutic protein over time. This includes profiling the expressed protein and identifying critical quality attributes (CQAs) through

  • extraction of a representative sample from the patient,
  • quantification of therapeutic expression levels over time,
  • profiling of attributes of the expressed product, and identification of correlations to outcome,

which can guide the selection and optimization of candidates and improve dosing decisions.

MS testing methods feature the highest possible analytical accuracy and sensitivity. Based on our comprehensive portfolio of MS-based methods we offer individual solutions for your specific requirements, partnering with you to develop analytical strategy, and/or deliver results for a single specific task.

  • Mass spectrometry
    • Peptide mapping
    • Intact molecular weight
    • Relative quantitation of viral proteins and ratio
    • Glycan profiling viral envelope proteins
    • HCP profiling

Additionally, we have established specialized testing packages for characterization and quality control testing such as

  • Capsid characterization
    • Percentage of full capsids (empty to full ratio)/partially full capsids
    • Identity of capsid proteins (VP1, VP2, VP3, truncated species, splice variants)
      • PTMs that correlate with stability/potency (deamidation, N-acetylation)
    • VP stoichiometry
    • Aggregation
  • Purity & identiy
    • Product concentration (protein, nucleotide, ratio)
    • Full-to-empty capsid ratio
    • Residual host cell proteins (HCPs)
    • Residual host cell DNA
    • Extended characterization
  • Process-related impurities
    • Residual processing enzymes
    • Stability & release testing

 

Protagen Protein Services partners you in establishing a comprehensive understanding of your product’s nature from harvest to approval. Applying mass spectrometry from an early stage on will significantly quicken your CGT product’s release process and enhance its chance of success.