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

Abstract

BACKGROUND:

p53 accumulation in head and neck squamous cell carcinoma (HNSCC) cells creates a targetable tumor antigen. Adjuvant dendritic cell (DC)-based vaccination against p53 was tested in a phase I clinical trial.

EXPERIMENTAL METHODS:

Monocyte-derived DC from 16 patients were loaded with two modified HLA-class I p53 peptides (Arm 1), additional Th tetanus toxoid peptide (Arm 2), or additional Th wild-type (wt) p53-specific peptide (Arm 3). Vaccine DCs (vDC) were delivered to inguinal lymph nodes at three time points. vDC phenotype, circulating p53-specific T cells, and regulatory T cells (Treg) were serially monitored by flow cytometry and cytokine production by Luminex. vDC properties were compared with those of DC1 generated with an alternative maturation regimen.

RESULTS:

No grade II-IV adverse events were observed. Two-year disease-free survival of 88% was favorable. p53-specific T-cell frequencies were increased postvaccination in 11 of 16 patients (69%), with IFN-γ secretion detected in four of 16 patients. Treg frequencies were consistently decreased (P = 0.006) relative to prevaccination values. The phenotype and function of DC1 were improved relative to vDC.

CONCLUSION:

Adjuvant p53-specific vaccination of patients with HNSCC was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity. HNSCC patients' DC required stronger maturation stimuli to reverse immune suppression and improve vaccine efficacy.

• Authors: Patrick J Schuler, Malgorzata Harasymczuk, Carmen Visus, Albert Deleo, Sumita Trivedi, Yu Lei, Athanassios Argiris, William Gooding, Lisa H Butterfield, Theresa L Whiteside, Robert L Ferris
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 9 Pg. 2433-44 (May 01 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24583792 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2014 AACR.

Chemical References

• Cancer Vaccines
• Cytokines
• Peptide Fragments
• Tumor Suppressor Protein p53

Topics

• Adult
• Aged
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Carcinoma, Squamous Cell (genetics, immunology, mortality, pathology, therapy)
• Cytokines (biosynthesis)
• Dendritic Cells (immunology, metabolism)
• Head and Neck Neoplasms (genetics, immunology, mortality, pathology, therapy)
• Humans
• Immunophenotyping
• Immunotherapy (adverse effects)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Middle Aged
• Neoplasm Staging
• Peptide Fragments (immunology)
• Phenotype
• Squamous Cell Carcinoma of Head and Neck
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Treatment Outcome
• Tumor Suppressor Protein p53 (chemistry, immunology)
• Vaccination