Last week, the San Francisco, California based developer announced what it says was an industry first for single-cell analytics in the GMP clinical space with Avance Biosciences, on behalf of a biotech client. The company reported the first tech transfer of a clinical trial-ready cell and gene therapy (CGT) assay from its Tapestri Platform to that CRO based in Houston, Texas.
Assessing the safety and efficacy of CGT products is more challenging than conventional therapies because of the many potential variations between genetically altered cells, reported Mission Bio. Cells modified with a viral vector will differ in transduction efficiency and the number of copies incorporated into the genome, while cells modified with tools like CRISPR can vary in on- and off-target edits, zygosity, or aberrant translocations, it said.
Before Tapestri, workflows required synchronizing data from multiple genotypic and phenotypic assays over several weeks, an approach with reduced specificity and limited ability to characterize cells with simultaneous edits, according to Mission Bio.
Its platform, it continued, will allow Avance to analyze cells that have been transduced with lentivirus, identifying transgene integration within individual cells without the need to grow clonal populations.
Brittany Enzmann, PhD, marketing manager, Mission Bio, told BioPharma-Reporter the platform allows the assessment of transduction efficiency at single-cell resolution, and eliminates certain processing steps.
“In many cell and gene therapies, viral vectors are used to transport therapeutic transgenes into cells. Yet, the efficiency of this process may vary from cell to cell.
“Tapestri can analyze DNA from thousands of individual cells in a single assay. In conventional cell or gene therapy analytical workflows, obtaining information at this resolution requires cells to be separated and clonally outgrown – a process that takes weeks and is limited to smaller sample sizes
“Because of Tapestri’s microfluidic and barcoding system, Avance can bypass the clonal outgrowth steps, meaning thousands of individual engineered cells can be analyzed in parallel in days, instead of weeks. Time is of the essence because most patients receiving cell therapies today have progressive cancer and have already failed multiple lines of treatment.”
Validation in GMP environment
The qualification and adoption of Tapestri assays – already used in pre-clinical settings to assess critical quality attributes of cell and gene therapy candidates – in a GMP environment validates their utility at the clinical and chemistry, manufacturing, and control (CMC) phases, said the company.
With GMP compliance, Tapestri can be used for batch release assays to assess products prior to administration to patients.
“With validation in a GMP environment, we hope to see widespread adoption soon, as the need is acute.
“In many ways, the rapid development of new cell and gene therapies has outpaced our ability to adequately characterize them. The US Food and Drug Administration (FDA) has predicted it will be approving between 10-20 CGT products per year by 2025, and a recent review showed that, over the past five years, more than half of CGT therapies using viral vectors were disrupted late in clinical development.
“Safety, efficacy, and CMC issues are disproportionately to blame for these disruptions, and better characterization is key to improving these outcomes, so drug developers and manufacturers understand exactly what is in their therapies,” noted Enzmann.
How have other customers been leveraging Tapestri?
“Mission Bio’s Tapestri is the only multi-omics platform that can simultaneously assess DNA and protein in thousands of individual cells. Even before Mission Bio introduced the CGT suite last fall, single-cell multi-omics with Tapestri had become an invaluable research tool for assessing genotype and phenotype at high resolution for both solid tumor and heme-onc research.
“With Tapestri Cell & Gene Therapy Solutions, customers using viral vectors have been able to measure vector copy number and transduction efficiency, while others using gene-editing tools like CRISPR have been able to quantify on-target edits alongside off-target and translocation events," she commented.