Phase I adjuvant trial of multi-epitope p53 vaccine for patients with squamous cell carcinoma of the head and neck (SCCHN): A pr

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Author(s): P. Andrade, A. Deleo, C. Visus, L. Butterfield, A. Argiris, R. L. Ferris; University of Pittsburgh Cancer Institute, Pittsburgh, PA
Alteration in the tumor suppressor protein, p53, is one of the most
common events in human cancers. Since most mutations of p53 are
associated with accumulation of p53, the nonmutated portions of protein
are readily accessible to degradation into wild type (wt) sequence
peptides for immune recognition by T lymphocytes.
Methods: A
phase I trial was conducted in stage I-IVa patients (pts) with SCCHN
with no active disease using autologous dendritic cells (DC) loaded
with two HLA-A*0201-restricted T cell-defined p53 peptides alone (Arm
1, 5 pts), plus either a wt p53 helper peptide (Arm 2, 5 pts) or
nonspecific helper peptide (dervied from tetanus toxoid, Arm 3, 6 pts).
The accrual goal is 24 patients, divided into the 3 arms. Each pt
received 3 intranodal vaccinations at 2-week intervals. The primary
endpoint was immunological response using ELISPOT, tetramer or delayed
type hypersensitivity (DTH)reactions to p53 peptides.
16 pts have been vaccinated so far. Erythema or hematoma were observed
at vaccine injection sites in two pts. At 15-mo median follow-up, 11/16
pts are alive without evidence of disease, 2 developed disease
recurrence, and 1 pt developed a second primary lung cancer. Two have
died of unrelated causes. Immunological analyses of the SCCHN patients'
responses to immunization indicate responses to both HLA-A2 binding
peptides. Tetramer frequencies for p53-specific CTL or IFN-gamma
ELISPOT assays indicated a 5/16 responders. Ongoing correlative
analyses include characterization of human papillomavirus (HPV)
infection, HLA, antigen processing machinery, and staining with soluble
T cell receptor for HLA-A2-p53 peptide complexes on tumor cells.
Adjuvant p53 peptide-loaded DC-based vaccination is feasible and safe
in pts with SCCHN. A phase II wt p53-based vaccine trial will be
proposed based on the most efficacious regimen used in this trial.