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Property "Has original text" (as page type) with input value "One disadvantage of the DCVax approach is that it requires that brain tissue be extracted from individual patients in order to make the vaccine. An alternative approach has been used by Dr. Black’s team at Cedars Sinai. Dendritic cells are still drawn from the peripheral blood of individual patients, but instead of tumor tissue lysate being mixed with those cells, a collection of six proteins typical of of GBMs is mixed with the
dendritic cells, creating an immune response to those antigens, with the mixture then returned to the patient via vaccinations. In a phase I trial (158), 20 GBM patients (17 newly diagnosed, 3 with recurrent tumors) received three vaccinations two weeks apart. Median PFS was 16.9 months, and median overall survival was 38 months. At the time of the clinical trial report, six of the patients had shown no sign of tumor recurrence. A later follow-up was reported in a Press release from ImmunoCellular Therapeutics (159), the biotech company sponsoring the vaccine (now called ICT-107). Survival rate at three years was 55%, with 38% of patients showing no evidence of recurrence, The most
recent update of the clinical trial (160), presented at the 2013 meeting of the World Federation of Neuro-oncology, reported that 7 of the original 16 patients in the trial were still alive, with survivals ranging from 60 to 83 months. One additional patient who was still tumor free after five years died from leukemia.
Currently ongoing is a randomized phase II trial, the interim results of which have recently reported by ImmunoCellular Therapeutics (161). Despite the impressive results described above, there was no statistically significant difference in median survival between the vaccine group and those treated with a placebo, although there was a numerical 2-3 month advantage for the vaccine group. However there was a similar difference in progression-free survival, which was statistically significant. The company emphasized that the results were preliminary and that they expected the difference in progression-free survival to translate into differences in overall survival with longer follow-up. However, the results also suggest that median survival and percentage of long-term survivors may be only weakly correlated due to the possibility that only a minority of patients benefit from the treatment, but those who do benefit a great deal.
Updated data from the phase II ICT-107 trial were presented on June 1, 2014 at the annual ASCO meeting (309). An important conclusion to be drawn from the new data is that mainly patients positive for HLA-A2 (a variant of the Human Leukocyte Antigen-A gene) seem to derive significant benefit from the vaccine. HLA are antigen-presenting proteins found at the cell surface. HLA-A2 is the most common variant in North America and Europe according to the press release and this group comprised 62% of patients randomized in this trial. The updated results are presented only for HLA-A2 positive patients, with results further subgrouped according to MGMT methylation status. Survival results in this trial are measured from the time of randomization after chemoradiation, and average time from initial surgery to randomization was 83 days (2.7 months).
For HLA-A2 positive patients with unmethylated MGMT, the ICT-107-vaccinated group had a median 4-month survival advantage compared with the placebo-vaccinated group. The ICT-107 group also had a median 4.5 month advantage in progression-free survival. These advantages in the vaccine-treated group did not reach statistical significance, though that is perhaps due to the small numbers of patients within these subgroups. 21% of ICT-107 treated patients were still alive at the time of the analysis, compared with only 7% of the placebo-treated patients.
Median survival has not yet been reached in the HLA-A2 positive, MGMT methylated group, though in this subgroup, ICT-107 treatment led to a dramatic and statistically significant increase in median progression-free survival: 24.1 months versus 8.5 months in the placebo-treated group. It is likely that this huge improvement in median progression-free survival in this subgroup will translate into significant median overall survival improvement.
Sadly, in June 2017, Immunocellular Therapeutics announced that their phase 3 ICT-107 trial was suspending recruitment due to insufficient funding. In the press release it was stated the company was looking for a partner for collaboration or acquisition of its ICT-107 program, and they were also taking steps to ensure the continued follow up of patients already being treated in the trial." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
