How new approaches to VCN and cell enumeration are optimizing cell therapy clinical testing

July 16, 2024

Laïla-Aïcha Hanafi, PhD

Cell therapy targets, constructs, and agents are expanding and diversifying — fast. Clinical testing must now comprehensively characterize an ever-broader number and array of therapies, while continuing to prioritize urgency and efficiency in their development and approval.

We delve into how clinical testing is evolving to meet demand in this rapidly changing landscape in our Cell Therapy Trends Report, and examine a few key areas where cell therapy testing programs are changing. One of these is cell enumeration and vector copy number (VCN) determination, which provide insights on how a given therapeutic construct is behaving in the body.

Below, we explore how techniques for cell enumeration and VCN determination are being adapted to assess greater numbers of increasingly complex and diversified therapy candidates, and discuss what the future holds for this key area of clinical testing.

Understanding cell enumeration and VCN in clinical testing

Cell enumeration and VCN determination methods assess cell number (via flow cytometric detection of surface proteins) and the number of constructs transduced into a cell (via PCR-based quantification of DNA), respectively. Together, the two measure cell therapy expansion and determine the abundance and persistence of therapeutic cells — crucial to ascertain how various cell types are responding to a therapy.

As cell therapies and sample types diversify, clinical testing for cell enumeration and VCN determination must assess a broader array of targets, requiring more specialized means of analysis. However, developers must also keep speed in mind, and balance specialization with efficiency to ensure that therapies are evaluated in a timely way.

So, what does the future hold for this realm of clinical testing?

Complementary methods

Cell enumeration and VCN determination techniques take complementary measurements from different angles, using different methods and analytes to evaluate cell therapies.

By utilizing both approaches in early-phase trials, cell therapy developers can gain high confidence in how they are interpreting their data, thereby producing a more reliable and robust picture of therapy expansion, and also lending confidence to each individual assay.

Alignment can also streamline testing. Cell enumeration via flow cytometry, despite providing additional phenotyping information on expanded cells, can be difficult to scale up, and so is often limited in later-stage use due to the challenges of collecting and transporting samples off-site. But, if aligned with cell enumeration in early-phase testing, VCN can act as a proxy measure of cell number during later-stage testing, simplifying logistics.

Increasing customization

As more diverse cell therapies reach clinical stages, cell enumeration and VCN determination methods need increasing customization — to track proprietary constructs as patients become more likely to receive multiple therapies, for instance. Additionally, new therapeutic cells such as CAR-macrophages may require novel antigen targets to be monitored in various tissues other than circulating blood, requiring new protocols for collection and analysis.

Enhancing modularity

Although customized assays are valuable, they are time- and resource-consuming to develop and validate. Modularization can minimize the timeline impact of assay customization. Testing programs for cell enumeration and VCN determination can be made quicker and easier to deploy by identifying generic analytes; and by utilizing modular data analytics to streamline readouts, and accelerate data processing.

Cell enumeration and VCN in the ever-changing cell therapy landscape

With the accelerating pace and increasing diversity of cell therapy development, clinical testing must become more responsive and adaptive, leveraging different approaches to deliver readouts that provide meaningful insights into cell therapy action and host response.

We dig deeper into emerging testing approaches for cell enumeration and VCN determination, and explore the future of cell therapy clinical testing more generally, in our Cell Therapy Trends Report. Download the report now, or contact our team to speak to an expert about your cell therapy needs.

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