Epitope identification and clinical immune monitoring in oncology programs

Epitope identification has emerged as a crucial stepping stone to study immune responses. It aids the discovery of targets for the development of new therapeutics and vaccines but can also identify potential areas of a therapeutic that are likely to generate neutralising anti-drug antibodies resulting in failure of treatment. Crucially, as antigen-specific immune responses are being routinely monitored to investigate the efficacy of a given treatment, thorough epitope mapping has dramatically enhanced the efficiency of these studies by flagging relevant epitopes to use for immune-monitoring, optimising the use of researchers time and resources and saving precious patient samples. Recently, we have contributed to confirming the success of ParvOryx, the first phase I/IIa clinical trial employing oncolytic rodent protoparvorirus to treat patients with recurrent glioblastoma. Using our mass-spectrometry-based ProPresent® Antigen Presentation assay on parvovirus-infected glioma cell lines, we have identified a panel of epitopes that are derived from both glioma cancer cells and the parvovirus. This has subsequently allowed the monitoring of antigen-specific immune responses by functional IFNγ ELISPOT. Results have shown that the majority of patients mounted an antiviral-specific response, demonstrating responsiveness to the treatment. Furthermore, some patients have also shown a low yet significant response to glioma antigens which could partially account effectiveness of treatment and for the positive clinical outcome of the trial. In this talk, we will also be detailing how epitope identification and immune monitoring multimers are powerful tools to boost the advancements of other gene therapy approaches notably Adeno-associated viruses and HSV.