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. Methods Monocyte-derived DC from 16 patients were loaded with two modified HLA-class I p53 peptides (Arm 1); additional T-helper(Th) tetanus toxoid peptide (Arm 2) or additional Th wt p53-specific peptide (Arm 3). Vaccine DC (vDC) were delivered to inguinal lymph nodes at 3 time points. Vaccine (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 to those of DC1 generated with an alternative maturation regimen. Results No grade II-IV adverse events were observed. Two-year disease-free survival (DFS) of 88% was favorable. p53-specific T-cell frequencies were increased post vaccination in 11/16 patients (69%), with IFN-γ secretion detected in 4/16 patients. Treg frequencies were consistently decreased (p=0.006) relative to pre-vaccination values. The phenotype and function of DC1 were improved relative to vDC. Conclusion Adjuvant p53-specific vaccination of HNSCC patients 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.

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

“…A phase I trial has been conducted in stage I-IVa patients with HNSCC with no active disease using a DC vaccine loaded with two HLA-A*0201-restricted T cell-defined p53 peptides alone, plus either a wt p53 helper peptide or nonspecific helper peptide derived from tetanus toxoid. In this study, diseasefree survival was 88% and p53-specific T cell frequencies were increased in approximately 70% of patients, whereas toxicity was acceptable (77). Finally, in another study, autologous DCs loaded with apoptotic tumor cells were injected intranodally in patients with advanced HNSCC; immunological responses were satisfactory and all patients were long term survivors (78).…”

Anticancer Dendritic Cell Vaccines Producing effective Antitumor T Cell Responses

“…In addition, vaccination led to decreased Treg levels. Two-year disease free survival was observed in 88% of vaccinated patients [39]. In another study, intranodal vaccination with apoptotic tumor cell-loaded DCs was well tolerated in all vaccinated patients with stage III/ IV HNSCC, and disease-free survival was more than five years [40].…”

Dendritic Cell Vaccine and its Application in Cancer Therapy

“…DCs pulsed with hypochlorous acid-oxidized tumor lysate were found to be safe and two of five vaccinated ovarian cancer patients experienced durable progression-free survival of 2 years and more after DC vaccination [22]. Vaccination of 16 patients with head and neck squamous cell carcinoma with DCs loaded with the tumor peptide p53 was associated with two-year disease free survival of 88% of vaccinated patients [43]. Injection a tetanus/ diphtheria toxoid in the vaccine site one day before vaccination with DCs pulsed with CMV phosphoprotein 65 RNA resulted in improved lymph node migration of DCs and prolonged survival of patients with glioblastoma.…”