Cellular Technology Limited
The ELISPOT Technology Pioneers

For more than twenty-five years, Cellular Technology Limited (CTL) has pursued the Mission to elevate ELISPOT to an exact science. The Cleveland-based company with its European headquarters, based in Bonn, Germany (CTL Europe GmbH), was the first to establish instrumentation and software that helped to advance ELISPOT from a subjective, low throughput research tool applied in a few specialized academic laboratories to an objective, automated high throughput technology for cell-mediated immunity monitoring.

When Prof. Dr. Paul V. Lehmann, founder & CEO of CTL & CTL Europe GmbH started his initial work in the field, ELISPOT results could be evaluated only visually, that was inevitably subjective, inaccurate, and cumbersome. Even when automatic image analysis was first applied to this end, the results were highly variable as the counting parameters needed to be set subjectively at the beginning.

Since objective, accurate, and reproducible measurements are fundamental to science, major efforts have been undertaken over the last two decades at CTL to understand the scientific principles behind ELISPOT data and develop intelligent image analysis algorithms based on these principles.

Consequently, spot recognition and spot-gating algorithms were engineered by the in-house software engineers closely collaborating with CTL’s R&D department, researching new software solutions for the automatic recognition of the signatures of defined cell populations, such as T cells vs. irrelevant cell types and noise. Pioneering software and instrumentation development in the ELISPOT field, CTL and hence CTL Europe GmbH were able to provide the ELISPOT analysis platform that in the mean time has become the gold standard in the field of immune monitoring.

As ELISPOT assays have become prevalent for monitoring antigen-specific T-cell immunity in clinical trials, the need to make data analysis objective, transparent, reproducible, and tamper proof adhere to Good Laboratory Practice (GLP) and Code for Federal Regulations (CFR) Part 11 guidelines, has surfaced.

CTL’s ELISPOT technology allows researchers to generate secretory footprints of antigen-specific T cells in the form of colored/ fluorescent spots in 96 or 384 well-plates

In addition, ELISPOT assays in both clinical and basic science environments require high throughput and automation, further raising the need for advanced data management and statistical analysis. The CTL software portfolio has been designed specifically for ELISPOT data analysis, management, and documentation.

The ELISPOT assay is particularly useful in areas where the measurement of low frequency ex vivo T cell responses is required. Such is the case for the development of a better understanding and the subsequent treatment of allergies and autoimmunity, for the ability to predict rejection/acceptance responses in organ transplantation, to improve drug and vaccine development, and to monitor various cancer treatments. CTL’s greatest strength lies in its high-throughput T cell and B cell immune monitoring capabilities and world-class ELISPOT expertise.

“CTL’s ELISPOT technology allows researchers to generate secretory footprints of antigen-specific T cells in the form of colored/fluorescent spots,” adds Dr. Lehmann. These spot images are then scanned, counted, and statistically evaluated. This method is used to determine whether a tested individual/patient responds positively or negatively to a drug, vaccine, or treatment and allows extended quantitative and qualitative measurements of each person’s immune response. CTL has years of experience in contracted research; many pharmaceutical, and biotechnology companies have been entrusting the enterprise with evaluating cell mediated immunity of their vaccines, drugs, and biological products using the ELISPOT technology. Having developed, optimized, qualified, and validated methods for immune monitoring in various test systems, CTL has a wealth of expertise encompassing a wide range of assay types in non-regulated and regulated environments. “We have a GLP-compliant laboratory capable of testing hundreds of samples per day,” states Dr. Lehmann. This immune monitoring allows CTL to speed up the development process for vaccines entering the clinical testing phase.

Dr. Lehmann believes that within the next years the implementation of ELISPOT research will make the transition from being done only by expert immunologists to essentially anyone who requires immune monitoring data. CTL Europe GmbH already now provides training, installations, simplified workflows, software, as well as data analysis tools to make the technique accessible to non-experts.