Dr. Paul V. Lehmann, Founder & CEO
For over twenty years, Cellular Technology Limited (CTL) has been on a mission to elevate ELISPOT to an exact science. The Cleveland-based company was among the first to establish instrumentation and software that helped to advance ELISPOT from a research tool available to a limited number of science labs to the automated high throughput technology for cell-mediated immunity monitoring in clinics.
When Dr. Paul V. Lehmann, founder and CEO of CTL 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 in Dr. Lehmann’s lab (or at CTL), the results were highly variable if the counting parameters were set subjectively. Since objective, accurate, and reproducible measurements are fundamental to good science, major efforts have been undertaken over the last decade 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 to automatically recognize the signatures of defined cell populations, such as T cells and identify them from irrelevant cell types and noise.
As ELISPOT assays have become the gold standard for monitoring antigen-specific T-cell immunity in clinical trials, the need to make data analysis objective, transparent, reproducible, and tamperproof, and adhere to GLP and Code for Federal Regulations Part 11 guidelines, has surfaced.
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. The T cell readout at a single-cell resolution is needed for the development of a better understanding and the subsequent treatment of allergies and autoimmunity. It is critical 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 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 in 96 or 384 well-plates. 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 entrusted CTL with evaluating cell-mediated immunity of their vaccines, drugs, and biological products using the ELISPOT technology. Having developed, optimized, qualified, and validated methods of the 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 processing 150 samples per day and up to 450 samples per week,” states Dr. Lehmann. This allows CTL to speed up the development process for vaccines entering the clinical testing phase and the subsequent immune monitoring.
Dr. Lehmann believes that within the next years the implementation of ELISPOT research will make the transition from being done by only expert immunologists to essentially anyone who requires immune monitoring data. CTL already now provides simplified workflows, software, as well as data analysis tools to make the technique accessible to non-experts.