Sponsored Content by Cerba ResearchReviewed by Louis CastelJan 30 2025
A well-designed CAR+ T assay should be capable of reporting an accurate set of data for its intended use. The assay’s validation parameters will depend on its intended use and any relevant regulatory requirements. This is done using the fit-for-purpose principle.
With its intended use defined, the next stage of CAR+ T assay development is the selection of specimen type; for example, whole blood, bone marrow aspirate or PBMC.
The choice of the specimen depends on several factors, such as the feasibility of local acquisition, the need for absolute counts, the need to run in batches, the presence of the population of interest, and the overall stability of the relevant study parameters.
PBMC is widely regarded as the most suitable specimen type in cases where stability issues hinder the global shipment of fresh material or when there is a need for batch testing.
PBMC preparations can also enable enrichment, which is a useful tool when looking to monitor CAR+ T cells in heavily lympho-depleted patients, such as those undergoing allogeneic CAR+ T therapy.
The selection of reagents is also a key aspect of any assay development. When working with CAR+ T PK assays specifically, the potential to reach high sensitivity is closely linked to the performance of the anti-CAR detection antibody.
Anti-idiotype monoclonal antibodies are highly recommended because these exhibit a high affinity for CAR+ T and exhibit a low nonspecific binding.
These reagents require customized development, however. It is also difficult to manage stocks of these reagents in global trials due to the combination of an extended manufacturing period, risks of inter-lot variability, and unpredictable elements within the sample forecast.
Commercial antibodies, such as target fusion proteins or anti-tag monoclonal antibodies, are, therefore, regarded as a more viable alternative from an operational perspective.
The characteristics of the CAR+T product itself should also be considered when designing the gating strategy. Two types of CAR+ T therapies exist: autologous and allogeneic.
Autologous CAR+ T-cells are acquired from the patient before being transduced and then infused into the same patient. Gating can be done with CD3-positive T-cell selection in this instance.
In contrast, allogeneic CAR+ T-cells require a different gating strategy because these are genetically knocked out in order for the CD3 T-cell receptor to reduce graft versus host risks.
It is also important to actively minimize any risks of interference with antibody-based therapies targeting markers of interest in the assay, such as anti-CD38 or PD1/PDL1 inhibitors. Clones of any reagents used in assays should be chosen based on their compatibility with the patient’s ongoing treatment.
Assay development and validation by Cerba Research
Cerba Research offers its customers customized panel design and fit-for-purpose validation with the option to fine-tune its products to accommodate specific patient samples.
The company approaches each project as a scientific collaboration between itself and the sponsor, encouraging open communication and full transparency in terms of relevant validation data, SOPs, and reports.
Image Credit: Cerba Research
An assay will be initially validated in the European Union or United States before being transferred and implemented around the world, in line with the needs of the trial in question.
Cerba Research’s flow cytometry capabilities extend around the globe, with laboratories in Africa, Australia, Europe, the United States, Taiwan, and China. The 12C BD Lyric platform is available across almost all of its sites (specifically Australia, Europe, the United States, and Asia), allowing the organization to offer consistent transparency across the globe.
Alongside its work in instrumental standardization, Cerba Research works with global standardized validation procedures, SOPs, and acquisition and analysis templates.
In addition to its standard use of the 12C BD Lyric instruments, the company offers flow cytometry via other platforms, including +40 multi-color flow on the Cytek Aurora throughout the European Union and the United States.
Analysis of sample data from a study is centralized in order to ensure alignment throughout the analysis team, project turnaround time is agreed upon before the project commences, and data transfer is fully automated via Cerba Research’s own in-house data platform.
Acknowledgments
Produced from materials originally authored by Ans De Beuckelear, Ph.D., and Rowan Claeys from Cerba Research.
About Cerba Research
For over 35 years, Cerba Research has been setting the industry standard for exemplary clinical trial conduct. Today, across five continents, with a focus on precision medicine, we are changing the paradigm of the central lab’s role in complex clinical research.
From protocol inception through development and to market, our passionate experts deliver the highest quality specialized and personalized laboratory and diagnostic solutions. Partner with us for the most efficient strategy to actualize your biotech and pharmaceutical products sooner and improve the lives of patients worldwide.
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