Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA)—An Accurate and Rapid Potential Companion Diagnostic and Pharmacological Interrogation Solution for Cancer Immunotherapy (PD-1/PD-L1)

Abstract

Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are a critical component for determining the safety and efficacy of newly developed ICBs for cancer treatment. In this study, we strive to demonstrate the feasibility of using hollow fiber assay microtube array membrane (MTAM-HFA) in the screening of anti-cancer ICBs. The MTAM-HFA process was carried out by encapsulating peripheral blood mononuclear cells (PBMCs) and the target cancer cells (cell lines or primary cells) and subcutaneously implanting them into Balb/C mice. At predetermined time points combination regimens of PD-1/PD-L1+ were administered accordingly and at a predetermined time point, the MTAMs were retrieved, and cell viability assays were carried out. The outcomes of the MTAM-HFA were compared against the clinical outcome of patients. Clinical comparison demonstrated excellent correlation between the screening outcome of MTAM-HFA of PD-1/PD-L1+ combination therapy and the clinical outcome of the lung cancer patients. Basic cell studies revealed that the utilization of MTAM-HFA in PD-1/PD-L1+ combination therapy revealed enhanced T-cell activity upon the administration of the PD-1/PD-L1 drug; thereby resulting in the reduction of tumor cell viability by up to 70%, and the cytotoxic effects by 82%. The outcome was echoed in the in vivo cell studies. This suggested that the MTAM-HFA system is suitable for use in PD-1/PD-L1+ screening and the accuracy, rapidity and cost effectiveness made it extremely suitable for application as a companion diagnostic system in both personalized medicine for cancer treatment and could potentially be applied to screen for candidate compounds in the development of next generation PD-1/PD-L1+ combination therapies.