Gene Therapy and Cell Therapy: Bioanalytical Challenges and Practical Solutions

Clinical development of gene therapy (GTx) and cell therapy (CTx) modalities involve extensive and challenging immunogenicity and pharmacokinetic assessments. The challenges associated with immunogenicity assessment are attributed to the unique delivery systems and complex nature of the immune responses against these multicomponent drug modalities. Many challenges for the immunogenicity assays are largely rooted in the critical reagents and analytical technology availability. Since viral vectors are commonly used for gene therapy, bioanalytical method development focusing on the assessment of pre-existing and drug-induced humoral anti-drug antibody (ADA) and cellular responses against adeno-associated virus (AAV) capsid and transgene expressed proteins require analytical technologies like the enzyme-linked immunospot (ELISpot) and flow cytometry beyond the conventional ligand binding assays (LBA) and liquid chromatography coupled mass spectrometry (LC-MS) platforms. Likewise, the bioanalytical strategy for chimeric antigen receptor (CAR) protein on CAR-T-cells also demands unique analytical platforms such as polymerase chain reaction (PCR). The regulatory expectations on bioanalytical technologies used for gene and cell therapy modalities continue to evolve. An industry consensus and regulatory guidance will help navigate through bioanalytical data and associated pharmacokinetics and immunogenicity data interpretation for these novel modalities.