Cell & gene therapies are used to treat both rare and common diseases. While gene therapy involves the transfer of genetic material, usually within a virus for uptake into diseased cells, cell therapy involves the transfer of genetically altered cells into a patient. As a global central laboratory services organization, we provide testing solutions for Cell & Gene Therapy clinical development programs. These include utilizing flow cytometry
, immunohistochemistry (IHC), cytokine profiling, immunogenicity and genomics
. With our industry-leading science and innovative solutions, we have experience partnering with clients to advance development of their cell and gene therapy trials across numerous indications and development phases.
CAR-T Cell Therapy
For treatment applications in Oncology, CAR-T (Chimeric Antigen Receptor T Cell) is a type of cell therapy which involves the introduction of T cells that have been genetically modified into the body of a cancer patient. CAR-T therapeutic development is now commonplace following recent approvals of drugs in CD19 expressing disease. These CAR-T products have been approved by the US FDA for certain types of leukemia and lymphoma, and both pharmaceutical and biotech companies are investing globally in this approach to treating cancer. The majority of cell and gene therapy testing solutions we have performed across our laboratories have been to support CAR-T development in US, Europe and China.
With CAR-T clinical development, because genetically modified T cells are used, the laboratory measurements for efficacy and safety can require innovative approaches. As living cells are used as the therapeutic vehicle, pharmacokinetic measurements require alternative methods. A cytokine storm, or an overproduction of immune cells and their activating compounds, often has associated safety issues, and a multitude of laboratory tests covering pro-inflammatory and cytokines, such as cytokine release assays, is required. With individual CAR-T programs, the genetic construct used is unique, and genomic methods used to assess persistence need to be validated. High-quality timely laboratory data is required to assist management of patients in CAR-T clinical trials, and to provide pharmaceutical and biotech companies with important information for regulatory filing, in addition for their own internal tollgate decision points. As these trials become global, Sponsors will need laboratories that can provide test results in their geographic region, as the cells tend to be genetically engineered and processed for infusion locally in that geographical region. A central laboratory is required to provide services from China, where CAR-T clinical development programs are increasingly abundant; the global central laboratory can validate locally for clinical trial testing, or it can receive the T cells as part of a technology transfer from its other global locations.
As a global laboratory services company supporting CAR-T clinical development programs, we provide flow cytometry, cytokine, genomic, bioanalytical & IHC testing for different intended uses including Expansion/Persistence (Pseudo PK), Efficacy, Prediction, Resistance, Safety, and Proof of Mechanism/Pharmacodynamics:
- Cell Expansion & Prolonged Treatment Persistence - determine if the CAR-T is present and what the absolute cell numbers are over the course of time
- Prediction – find if there is an immune signature likely to predict for response and if the target is expressed
- Efficacy – discover if the CAR-T is stimulating, infiltrating & proliferating
- Resistance – look for evidence of lack of target engagement or evidence of residual disease
- Safety – understand what the biological evidence is behind Cytokine Release Syndrome (CRS) and neurotoxicity
- Proof of Mechanism/Pharmacodynamics – seek evidence that the target is engaged to result in a biological change of the target and/or downstream effect
Our CAR-T Solutions
As CAR-T therapies proceed through clinical development, the requirement for clinical trial testing from multiple clinical trial centers increases, as does the need for central laboratory testing. Harmonized testing and proficiency provide added assurance for reproducible and accurate data. We provide a high level of laboratory testing to support cell & gene therapy approaches including CAR-T. Contact us for more information on the validation and testing approaches that we have adopted to evaluate safety and efficacy of this immuno-oncology therapeutic approach.