Serial Multi-omics Uncovers Anti-Glioblastoma Responses Not Evident by Routine Clinical Analyses (Global Proteomics)

Recurrent glioblastoma (rGBM) is incurable. Serial “multi-omic” assays from longitudinal rGBM biopsies may unravel tumor responses to a treatment. Despite traditional imaging indicating tumor progression, 86 serial rGBM biopsies cores obtained over 4 months from the first two patients on a clinical trial of repeated intratumoral doses of the immunotherapeutic agent, CAN-3110, revealed therapeutic effects by multi-omic analyses, including: a-longitudinal and spatial reshaping of the rGBM’s microenvironment, b- expansion of new T cell tissue-resident effector memory clonotypes against newly characterized CAN-3110 epitopes and other undetermined antigens, and c-novel expression of HLA-immunopeptides including cancer testes antigens. The two treated patients achieved a pathologic response or stable clinical disease, respectively. These results show the value of longitudinal tissue sampling to understand GBM’s evolution during an investigational therapy.