Phase I dendritic cell p53 peptide vaccine for head and neck cancer

Disease-feee survival

Disease-feee survival

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Summary

In this study Adjuvant dendritic cell (DC)-based vaccination against p53 was tested in patients with head and neck squamous cell carcinoma. Adjuvant p53-specific vaccination of HNSCC patients was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity.

Patients characteristics

16 HLA-A2.1+ patients with advanced head and neck squamous cell carcinoma (HNSCC) were enrolled in this study. Six patients were treated with surgery alone and 10 patients had received adjuvant chemo- radiotherapy (CRT) after surgery. At the time of vaccination, all patients were free of disease.

Methodology

Generation of DC
Monocytes were isolated from autologous leukapheresis products by the Elutra System. Following 6-day culture of separated monocytes, DC medium containing GM-CFS (1,000IU/mL) and IL-4 (10ng/mL), immature DC (iDC) were harvested and counted. Aliquots containing 10,000 harvested iDC were re-plated in T-75 culture flasks in medium containing GM-CFS and IL-4 as above and matured by the addition of a pro-inflammatory cytokine cocktail for 48 hours. DC used for vaccination of patients (vDC) were matured in a cytokine cocktail containing IL-1β (10ng/mL), IL-6 (10ng/mL), TNF-α (10ng/mL) and PGE2 (1ug/mL).

Treatment

Fresh or cryopreserved mDC were loaded with the respective combinations of class I / class II peptides (10uM each) for 18 hours. Autologous DC (100 uL) were injected into an inguinal lymph node (LN) under ultrasound guidance biweekly for three time points. LN in the head and neck region were avoided, as they could have been affected by the proximity of tumor cells.

Results

Adverse events
The vaccine was well tolerated by all patients, with skin rash at injection sites and circumscribed hematomas after leukapheresis in 2/16 patients, but no grade II-IV adverse events occurred. No differences were observed between vaccine arms. All patients were followed every 3 months using clinical examination and periodic PET/CT scans for 3 years.
Disease-free survival and tumor immunohistochemistry
Among the 16 vaccinated patients, 3 died of disease (DOD) at 16, 17 and 25 months; 13 patients remain alive with no evidence of disease (NED) the median follow-up of 32 months (range 6 – 42 months). Thus, two-year disease-free survival (DFS) was 88% and three-year DFS was 80%.

Conclusion

Adjuvant p53-specific vaccination of HNSCC patients was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity.

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Scientific article publishing date: 5/1/2014

Immucura identifier BSC21_317EN

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