Alpha-type-1 Polarized Dendritic Cell-based Vaccination in Newly Diagnosed High-grade Glioma: A Phase II Clinical Trial

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Summary

This study examines patients with Glioblastoma multiforme (GBM) and how they respond to a-type-1 Dendritic Cell vaccine. As a result a significant survival-prolonging effect was verified in DC-treated glioma patients. The vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen.

Patients characteristics

The sixteen newly diagnosed glioma patients, who consisted of 14 GBM (WHO grade 4- 5) patients, 1 anaplastic astrocytoma (AA) (grade 3) patient and 1 anaplastic oligodendroglioma (AO) (grade 3) patient,
represented 8 HLA-A2+ cases and 8 HLA-A24+ cases.

Methodology

Monocyte-enriched fractions were separated from leukapheresis products using OptiPrepTM and cultured in the presence of granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin (IL)-4 in X- VIVO15 serum-free medium. On day 5 of culture, TNF-α, IL-1β, IFN-α, IFN- γ, and poly I/C were added to the culture to obtain mature DC-enriched cultures. On day 7, the harvested cells were pulsed with a cocktail of 5 glioma-specific synthetic peptides that were restricted to HLA A2 or A24, and then with keyhole limpet hemocyanin (KLH). The DC- enriched cells were washed and cryopreserved in a Cryocyte bag until use.

Treatment

The patients received 3 intradermal DC vaccines in the posterior neck weekly, and then they received vaccines twice every 2 weeks; finally, they received them every month for 5 months. The dose range of the injected DCs was 1×5×107/patient/shot.

Results

The mean injected DC number was 2.2×107/patient, the DC injection time was 8.8 on average, and 11 cases involved 10 injections. No severe side effects higher than grade III were observed. After 6 years of observation since the initiation of the study, five patients were still alive, and two of these patients were relapse-free. The relapse-free time and overall survival time (median) were 11.0 months and 19.0 months, respectively.

Regarding the skin tests, positive DTH reactions against peptide and KLH were detected in 4 cases (27%) and 9 cases (60%), respectively, in vaccinated patients. Ten of the 15 evaluable cases (67%) showed positive ELISPOT reactions against any tumor antigen peptides, and 9 cases respondedto more than 2 peptides. The serum IFN-γ concentration measured with a sensitive ELISA kit was specifically increased in 6 cases (43%) to more than 10 ug/ml after the initiation of the DC vaccine trial.
RFS and OS

After six years of observation since the initiation of the study, five patients were still alive, and two remained relapse-free. The RFS and OS (median) were 11.0 months and 19 months, respectively; the RFS and OS (median) of the historical control group were 9.0 months and 16.0 months, respectively. The RFS and OS analyses revealed a significant survival-prolonging effect in DC-treated glioma patients.

Conclusion

In conclusion, Peptide-cocktail-pulsed α-type-1 DC vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen, which is partly based on IL-12-IFN-γ- mediated T-cell activation..

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Scientific article publishing date : 13/12/2016

Immucura identifier : BSC21_060EN

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