As the Bioanalytical support for drug development continues to grow, more and more scientists are requiring more complex assays. Two examples are cell based assays and what we refer to as live cell assays.
Typically a cell based assay requires culturing of cells for several days prior to being used in an assay. Live cell methods are whole blood samples that need to be analyzed within 24 -48 hours or require isolation and freezing of peripheral blood mononuclear cells (PBMCs) within 24-48.
A recent example of how impactful cell based assay testing for pharmacodynamics (PD) can be, in the fall of 2017 a client came to us with improperly collected PD flow cytometry data from a subset of patients for support of a phase I oncology trial. The client had a subset of patients that had tumor shrinking/regression and hypothesized that those patients had specific T-cell responses to the therapy. We designed an in-vitro stimulation method followed by a newly designed immunopheontyping and intracellular cytokine staining flow cytometry panel. Of the 10 patient PBMCs we screened by in vitro stimulation with a tumor peptide pool (n=4 peptides), 7 were positive responders (tumor regression/shrinkage) and 3 were non-responders. 6 of the 7 positive responders showed tumor peptide specific T-cell responses by flow cytometry. All 3 non-responders were negative for tumor peptide specific T-cell responses by flow cytometry.
The client shared that the survival of the patient directly correlated with the T-cell responses to the peptide pool. Further, client made a change in the adjuvant during the phase I trial to increase efficacy of the drug. The 3 non-responders (clinically and flow cytometrically) were dosed with the original adjuvant. All 7 clinically positive responders were given the new/improved adjuvant and 6 showed tumor specific T-cell responses by flow cytomtery. The client is asking us to screen the 6 positive patients for each of the four individual peptides to further understand the pharmacodynamics response in these patients.
When we had first met with the client they informed us that they were on the fence about moving forward to phase II, which is why they wanted PD results to help them make that decision. Client stated they plan to move forward with a phase II trial based on the results of the flow cytometry individual peptide results. What an amazing turnaround for the client and the patients who will benefit from this therapy.
We have expanded our cell culture suite at KCAS to support our clients’ cell based and live cell assay needs. We have 3 qualified methods for isolation of PBMCs that clients can select from for support of their clinical trials. Additionally, we have expanded our capabilities and are working on cell based biomarker imaging assays. Stay tuned!