Tissue and tumor sample testing are valuable matrix to test for drug levels (PK) and biomarkers (PD). They are understudied in my opinion as far too many studies result in no data or uninterpretable data. The root cause is a break down in how the tissue was collected, processed, and utilized for a PK or a biomarker assay. Not enough feasibility and development was performed to ensure you are generating reliable and defendable data. We at KCAS have the good fortunate of having been helping people develop drugs since 1979 and tissue analysis is one of our core expertise.
We help our partners with tissue analysis needs by leveraging our experience with automated homogenization, manual homogenization, optimization of homogenization buffers, and the long list of species and tissue types we have experience with (see tissue list link). We have done human studies looking at human nail clippings and nerves to pig bladders for PK analysis. PK Validation of those methods is an area where we can offer consultative services to assist our clients. The large molecule team at KCAS has been busy qualifying tissue and tumor Biomarker/PD assays. I want to share two experiences where our Tissue expertise significantly helped our partners.
A small biotech company shared with us the tissue processing method and the flow cytometry data that a lab had previously performed on tumors from a murine disease model. They shared the flow cytometry data the previous lab used and we immediately knew the issues. Samples were not properly processed for flow cytometric analysis. The improper processing resulted in the inability to detect the tumor cells and the hypothesized TILs (Tumor Infiltrating Lymphocytes) the client believed they were generating with their therapy. The client’s second study had already started and they needed a lab to be ready to process and analyze tumors in 3 weeks. We were able to successfully detect significant infiltration of TILs into the tumors and a reduction in the % of tumor malignant cells (See table below). This data was used to support an IND filing. Client was incredible thankful that they partnered with KCAS and there hypothesis proven true.
Table 1: Monitoring of Murine TILs and % Tumor cells
The second case study a large Biotech had been performing ‘legacy’ tissue biomarker assay in house for 7 years. Assay was burden on R&D resources and client needed rapid transfer and qualification to a CRO who could meet demand of turnaround time. Client is using pre-clinical results to make decisions for clinical trials. They had tried to transfer to two other CRO’s previously, however, with hundreds of samples waiting to be tested with hundreds more to be harvested they needed help. The internal team informed them it would take 6-7 months to test all the samples. The client had 7 total tissues they need analyzed for a biomarker. Four high priority tissues and three low priority tissues. The client partnered with KCAS to do a transfer of the method using one of the low priority tissues, the quadriceps. The original goal was for KCAS to test the low priority and the internal team test the high priority. We were able to transfer and qualify the assay in 6 weeks. The standard curve was expanded from 12.5 – 200 to 6.25 – 400ug/mL. The comparison data of forty left quads (performed by Client) compared to the right quad (performed by KCAS) was so compellingly similar that the client decided to have KCAS test all 7 tissue types (see Figure 1 below).
Figure 1: Tissue Comparative Study Results
We successfully tested and reported results for all their in-house samples in less than a month as we were able to stream line the procedure (See KCAS an Orchestrated Approach). KCAS has tested over 2,500 samples for support of 3 different studies without a single failed assay.
The two case studies above is a small glimpse into the tissue expertise the small and large molecule teams at KCAS possess. The LM team over the last year have been supporting numerous other tissue studies. Weather it is PK studies in brain and spinal cord homogenates or intracellular cytokine analysis of tumors, we have the knowledge, the instrumentation and experience to provide you with reliable and defendable data. We at KCAS get up every day and have the pleasure of being able to impact global health by helping our partners develop drugs. With a can do attitude and positive only approach we are solving problems and exceeding time lines.