The vaccine has shown a benign safety profile with minimal severe adverse effects, making it a potentially safer alternative or complement to existing GBM treatments.
[2,"smw-datavalue-wikipage-property-invalid-title","Has original text","One disadvantage of the DCVax approach is that it requires that brain tissue be extracted\nfrom individual patients in order to make the vaccine. An alternative approach has been\nused by Dr. Black\u2019s team at Cedars Sinai. Dendritic cells are still drawn from the\nperipheral blood of individual patients, but instead of tumor tissue lysate being mixed\nwith those cells, a collection of six proteins typical of of GBMs is mixed with the\n\ndendritic cells, creating an immune response to those antigens, with the mixture then\nreturned to the patient via vaccinations. In a phase I trial (158), 20 GBM patients (17\nnewly diagnosed, 3 with recurrent tumors) received three vaccinations two weeks apart.\nMedian PFS was 16.9 months, and median overall survival was 38 months. At the time of\nthe clinical trial report, six of the patients had shown no sign of tumor recurrence. A later\nfollow-up was reported in a Press release from ImmunoCellular Therapeutics (159), the\nbiotech company sponsoring the vaccine (now called ICT-107). Survival rate at three\nyears was 55%, with 38% of patients showing no evidence of recurrence, The most\n\nrecent update of the clinical trial (160), presented at the 2013 meeting of the World\nFederation of Neuro-oncology, reported that 7 of the original 16 patients in the trial were\nstill alive, with survivals ranging from 60 to 83 months. One additional patient who was\nstill tumor free after five years died from leukemia.\n\nCurrently ongoing is a randomized phase II trial, the interim results of which have\nrecently reported by ImmunoCellular Therapeutics (161). Despite the impressive results\ndescribed above, there was no statistically significant difference in median survival\nbetween the vaccine group and those treated with a placebo, although there was a\nnumerical 2-3 month advantage for the vaccine group. However there was a similar\ndifference in progression-free survival, which was statistically significant. The company\nemphasized that the results were preliminary and that they expected the difference in\nprogression-free survival to translate into differences in overall survival with longer\nfollow-up. However, the results also suggest that median survival and percentage of\nlong-term survivors may be only weakly correlated due to the possibility that only a\nminority of patients benefit from the treatment, but those who do benefit a great deal.\n\nUpdated data from the phase II ICT-107 trial were presented on June 1, 2014 at the\nannual ASCO meeting (309). An important conclusion to be drawn from the new data is\nthat mainly patients positive for HLA-A2 (a variant of the Human Leukocyte Antigen-A\ngene) seem to derive significant benefit from the vaccine. HLA are antigen-presenting\nproteins found at the cell surface. HLA-A2 is the most common variant in North America\nand Europe according to the press release and this group comprised 62% of patients\nrandomized in this trial. The updated results are presented only for HLA-A2 positive\npatients, with results further subgrouped according to MGMT methylation status.\nSurvival results in this trial are measured from the time of randomization after\nchemoradiation, and average time from initial surgery to randomization was 83 days (2.7\nmonths).\n\nFor HLA-A2 positive patients with unmethylated MGMT, the ICT-107-vaccinated group\nhad a median 4-month survival advantage compared with the placebo-vaccinated group.\nThe ICT-107 group also had a median 4.5 month advantage in progression-free survival.\nThese advantages in the vaccine-treated group did not reach statistical significance,\nthough that is perhaps due to the small numbers of patients within these subgroups. 21%\nof ICT-107 treated patients were still alive at the time of the analysis, compared with only\n7% of the placebo-treated patients.\n\nMedian survival has not yet been reached in the HLA-A2 positive, MGMT methylated\ngroup, though in this subgroup, ICT-107 treatment led to a dramatic and statistically\nsignificant increase in median progression-free survival: 24.1 months versus 8.5 months\nin the placebo-treated group. It is likely that this huge improvement in median\nprogression-free survival in this subgroup will translate into significant median overall\nsurvival improvement.\n\nSadly, in June 2017, Immunocellular Therapeutics announced that their phase 3 ICT-107\ntrial was suspending recruitment due to insufficient funding. In the press release it was\nstated the company was looking for a partner for collaboration or acquisition of its\nICT-107 program, and they were also taking steps to ensure the continued follow up of\npatients already being treated in the trial."]