Vaccine Therapy in Treating Patients With Head and Neck Cancer

Adjuvant p53 Peptide Loaded DC-Based Therapy for Subjects With Squamous Cell Cancer of the Head and Neck (A Phase I Safety and Immunogenicity Trial)

RATIONALE: Vaccines made from a person's dendritic cells mixed with peptides may help the body build an effective immune response to kill tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects of vaccine therapy in treating patients with head and neck cancer.

OBJECTIVES:

Primary

• Determine the toxicity of intranodally injected autologous dendritic cells (DC) loaded with wild-type p53 peptides with or without T-helper peptide epitope in patients with squamous cell carcinoma of the head and neck.

Secondary

• Determine the local and systemic immunomodulatory effects of this vaccine in these patients.

OUTLINE: This is a randomized, pilot study.

Patients undergo leukapheresis. The resulting dendritic cells (DC) are pulsed with wild-type (wt) p53 peptides with or without T-helper (Th) peptides. Individual autologous vaccines are prepared for each patient. Patients who are HLA-A2-DR4-negative are randomized to 1 of 2 treatment arms (arm I or arm II). Patients who are HLA-A2-DR4-positive are assigned to arm III.

• Arm I: Patients receive autologous DC loaded with HLA-A2.1-restricted wt p53 peptides only.
• Arm II: Patients receive autologous DC loaded with HLA-A2.1-restricted wt p53 peptides and Th tetanus toxoid peptide.
• Arm III (HLA-A2-DR4-positive patients only): Patients receive autologous DC loaded with HLA-A2.1-restricted wt p53 peptides and Th wt p53 peptide.

In all arms, each vaccine is administered by ultrasonography-guided inguinal intranodal injection over 30 minutes on days 0, 14, and 28.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck

  • Resectable disease
  • Any stage allowed

• Successfully treated with curative intent

• Recurrent disease allowed provided the following criteria are met:

  • No evidence of disease
  • At least 6 weeks since prior antitumor therapy

• Positive for HLA-A2.1

  • HLA-DR4 allele status known

• Tumor tissue must be available

• No active brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0 or 1
• Life expectancy ≥ 6 months
• Granulocyte count > 2,500/mm^3
• Lymphocyte count > 700/mm^3
• Platelet count > 100,000/mm^3
• Bilirubin < 0.2 mg/dL
• Creatinine < 0.2 mg/dL
• Hemoglobin > 8 g/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for ≥ 1 week before, during, and for ≥ 2 weeks after study completion
• No systemic infection or coagulation disorders
• No psychiatric disturbances that would preclude obtaining informed consent or safe conduct of protocol
• HIV negative
• Hepatitis B surface antigen and hepatitis C antibody negative
• No other active malignancies

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 6 weeks since prior adjuvant radiotherapy or chemoradiotherapy

  • No time restriction for prior curative therapy

• No concurrent pharmacological doses of steroids in any form (topical or systemic)