Int J Oncol. 2015 Apr;46(4):1699-709. doi: 10.3892/ijo.2015.2846. Epub 2015 Jan 23.
Immune responses in patients with esophageal cancer treated with SART1 peptide-pulsed dendritic cell vaccine.
1Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata 951‑8518, Japan.
2Department of Surgery, School of Medicine, Niigata University, Niigata 951‑8520, Japan.
3Department of Hematology, Endocrinology, and Metabolism, School of Medicine, Niigata University, Niigata 951‑8520, Japan.
4Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Fukuoka 830‑0011, Japan.
Patients with advanced stage of squamous cell carcinoma of esophagus have a poor prognosis with a lethal outcome. In order to explore the feasibility and effectiveness of dendritic cell (DC)-based immunotherapy for squamous cell carcinoma of esophagus, we performed a phase I/II clinical trial of monocyte-derived dendritic cells (moDCs) pulsed with SART1 peptide in seven patients with advanced stage of this disease. Although the feasibility of this therapy was definite, the effectiveness was not clearly confirmed in advanced stage of squamous cell carcinoma of esophagus. However, in vitro study revealed that moDCs generated for this therapy possessed a potent ability of inducing SART1 peptide-specific cytotoxic T lymphocytes (CTLs). In addition, these moDCs were demonstrated to be able to produce exosomes with an antigen presenting ability for inducing SART1 peptide-specific CTLs. ELISPOT assay using cryopreserved patient’s lymphocytes demonstrated that IFN-γ ELISPOTs were increased after four times of SART1 peptide-pulsed moDC vaccinations compared with before the vaccination in a patient. The present study demonstrated that moDCs prepared from advanced stage of squamous cell carcinoma of esophagus possess a good immune function and in vivo immune responses (detected by ELISPOT assay) were evoked by the infusion of these moDCs. These findings suggest that DC-based immunotherapy could be one of the modalities applicable for squamous cell carcinoma of esophagus.
Head Neck. 2010 May;32(5):626-35. doi: 10.1002/hed.21233.
Dendritic cells pulsed with GST-EGFR fusion protein: effect in antitumor immunity against head and necksquamous cell carcinoma.
1Department of Otolaryngology, 2nd Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
Overexpression of epidermal growth factor receptor (EGFR) is common in head and neck squamous cell carcinoma (HNSCC). Targeting EGFR is an effective approach to treat EGFR-positive HNSCC. However, the clinical benefits of the present EGFR-targeting agents are still limited in HNSCC patients.
Recombinant glutathione-S-transferase (GST)-EGFR fusion protein was produced and purified. Dendritic cells (DCs) of C3H mice were pulsed with fusion protein. Mice were challenged with HNSCC cells before or after vaccination with these DCs, and the cytotoxic T-lymphocyte (CTL) response, interferon-gamma (IFN-gamma) secretion, tumor growth, and survival of mice were assessed.
Significant in vitro and in vivo antitumor activities were observed for mice immunized with DCs pulsed with GST-EGFR fusion protein, compared with the control groups (p < .05).
The DCs pulsed with GST-EGFR fusion protein can provide not only preventive but also therapeutic antitumor activities against HNSCC in the animal model.
Clin Cancer Res. 2014 May 1;20(9):2433-44. doi: 10.1158/1078-0432.CCR-13-2617. Epub 2014 Feb 28.
Phase I dendritic cell p53 peptide vaccine for head and neck cancer.
1Authors’ Affiliations: Cancer Immunology Program; Biostatistics Facility, University of Pittsburgh Cancer Institute; Departments of Pathology and Otolaryngology, University of Pittsburgh School of Medicine; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Medicine, Hematology/Oncology, University of Texas-San Antonio Cancer Center, San Antonio, Texas; and Department of Otolaryngology, University of Ulm, Germany.
p53 accumulation in head and neck squamous cell carcinoma (HNSCC) cells creates a targetable tumor antigen. Adjuvantdendritic cell (DC)-based vaccination against p53 was tested in a phase I clinical trial.
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.
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.
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.