Science Times: Phase I/II Trial of Combination of Temozolomide Chemotherapy and Immunotherapy With Fusions of Dendritic and Glioma Cells in Patients With Glioblastoma

Standard treatment for newly diagnosed glioblastoma multiforme (GBM) includes surgical resection, followed by adjuvant radiation and concurrent temozolomide (TMZ) chemotherapy. Almost invariably, GBM acquires resistance to TMZ, resulting in tumor recurrence and clinical deterioration. The advent of immunotherapy may be a promising development in the treatment of GBM. One potential immunotherapeutic approach involves activation of antigen-presenting cells to mount a stronger antitumor response by effector CD4+ and CD8+ T-cells. Dendritic cells, the main antigen-presenting cells in humans, have been utilized as immunotherapeutic agents in GBM.1 For instance, Kikuchi et al2 showed that autologous injection of fusion cells (FC), created by fusing the patient’s glioma cells with his or her own dendritic cells, results in a potent antigen-presenting cells capable of powerful cytotoxic T-lymphocyte responses.

Based on the successful results of immunotherapy against GBM with FC, Akasaki et al3 evaluated the effects and clinical outcomes of a combined TMZ and FC chemo-immunotherapeutic approach. They investigated the effects of this approach in 2 groups: patients with recurrent primary glial tumors after surgical excision and adjuvant TMZ therapy (n = 10) and patients with newly diagnosed GBM (n = 22). The FC formulation was given intradermally in the cervical region 2 wk after the first maintenance TMZ-therapy and given at least 3 times in each 28-d cycle. Compared to the progression free survival (PFS) of 6.9 mo and overall survival (OS) of 14.6 mo in patients receiving adjuvant TMZ alone,4 patients receiving adjuvant TMZ and FC had more favorable outcomes. Patients with newly diagnosed GBM receiving TMZ + FC had a PFS of 13.7 mo and OS of 25.3 mo and patients with recurrent GBM receiving TMZ + FC had a PFS of 8.2 mo and OS of 12.6 mo.

Full access available to all Journal subscribers.