Allogeneic Natural Killer and Cytomegalovirus (CMV)-pp65 Pulsed Dendritic Cells Induced Complete Response Through 15 Months in a Patient with Recurrent Glioblastoma: A Case Study.

BACKGROUND Glioblastoma (GBM) is a highly aggressive brain tumor with poor survival outcomes. While conventional treatment strategies such as surgery, radiation, and chemotherapy can extend survival, the prognosis for GBM patients after 2 years remains low. One-year progression-free survival (PFS) and complete response (CR) with recurrent GBM is extremely low. Recent clinical trials using either engineered chimeric antigen receptor (CAR) T cells, autologous dendritic cell (DC) vaccination, or natural killer (NK) cells have shown promise for patients with GBM following initial diagnosis. Despite these significant immunotherapeutic advancements, new strategies need to be developed to address the poor survival outcomes for GBM. CASE REPORT A 36-year-old male patient with recurrent bilateral parietal GBM, following subtotal resection, was treated using an immunotherapeutic strategy combining lymphosuppressive conditioning with intravenous administration of highly purified allogeneic NK cells (mismatched for inhibitory killer Ig-like receptor [KIR]-human leukocyte antigen [HLA] ligand interactions), celecoxib, temozolomide (TMZ), tetanus-diphtheria vaccination, and multiple intradermal injections of human cytomegalovirus (CMV)-pp65 pulsed dendritic cells. This treatment did not exhibit any toxic effects and resulted in regression of intracranial residual disease on both hemispheres. Additionally, the clinical response was durable, persisting for more than 15 months after the first infusion of KIR-HLA-mismatched purified allogenic NK cells. CONCLUSIONS A patient with recurrent GBM achieved durable CR with a novel treatment strategy with allogeneic NK cells and DC pulsed with CMV-pp65 following subtotal surgical resection. If confirmed in additional patients, this combination approach could offer an effective therapeutic option for people with an otherwise dismal prognosis.