Phase i dendritic cell p53 peptide vaccine for head and neck cancer

Patrick J. Schuler, Malgorzata Harasymczuk, Carmen Visus, Albert De Leo, Sumita Trivedi, Yu Lei, Athanassios Argiris, William Gooding, Lisa H. Butterfield, Theresa L. Whiteside, Robert L. Ferris

Research output: Contribution to journalArticle

71 Citations (Scopus)

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 HLAclass 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-g 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.

Original languageEnglish (US)
Pages (from-to)2433-2444
Number of pages12
JournalClinical Cancer Research
Volume20
Issue number9
DOIs
StatePublished - May 1 2014
Externally publishedYes

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Subunit Vaccines
Head and Neck Neoplasms
Dendritic Cells
Vaccines
Peptides
Vaccination
T-Lymphocytes
Phenotype
Clinical Trials, Phase I
Tetanus Toxoid
Groin
Neoplasm Antigens
Regulatory T-Lymphocytes
Disease-Free Survival
Monocytes
Immunity
Flow Cytometry
Lymph Nodes
Cytokines
Carcinoma, squamous cell of head and neck

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schuler, P. J., Harasymczuk, M., Visus, C., De Leo, A., Trivedi, S., Lei, Y., ... Ferris, R. L. (2014). Phase i dendritic cell p53 peptide vaccine for head and neck cancer. Clinical Cancer Research, 20(9), 2433-2444. https://doi.org/10.1158/1078-0432.CCR-13-2617

Phase i dendritic cell p53 peptide vaccine for head and neck cancer. / Schuler, Patrick J.; Harasymczuk, Malgorzata; Visus, Carmen; De Leo, Albert; Trivedi, Sumita; Lei, Yu; Argiris, Athanassios; Gooding, William; Butterfield, Lisa H.; Whiteside, Theresa L.; Ferris, Robert L.

In: Clinical Cancer Research, Vol. 20, No. 9, 01.05.2014, p. 2433-2444.

Research output: Contribution to journalArticle

Schuler, PJ, Harasymczuk, M, Visus, C, De Leo, A, Trivedi, S, Lei, Y, Argiris, A, Gooding, W, Butterfield, LH, Whiteside, TL & Ferris, RL 2014, 'Phase i dendritic cell p53 peptide vaccine for head and neck cancer', Clinical Cancer Research, vol. 20, no. 9, pp. 2433-2444. https://doi.org/10.1158/1078-0432.CCR-13-2617
Schuler PJ, Harasymczuk M, Visus C, De Leo A, Trivedi S, Lei Y et al. Phase i dendritic cell p53 peptide vaccine for head and neck cancer. Clinical Cancer Research. 2014 May 1;20(9):2433-2444. https://doi.org/10.1158/1078-0432.CCR-13-2617
Schuler, Patrick J. ; Harasymczuk, Malgorzata ; Visus, Carmen ; De Leo, Albert ; Trivedi, Sumita ; Lei, Yu ; Argiris, Athanassios ; Gooding, William ; Butterfield, Lisa H. ; Whiteside, Theresa L. ; Ferris, Robert L. / Phase i dendritic cell p53 peptide vaccine for head and neck cancer. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 9. pp. 2433-2444.
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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 HLAclass 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-g 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.",
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AU - Harasymczuk, Malgorzata

AU - Visus, Carmen

AU - De Leo, Albert

AU - Trivedi, Sumita

AU - Lei, Yu

AU - Argiris, Athanassios

AU - Gooding, William

AU - Butterfield, Lisa H.

AU - Whiteside, Theresa L.

AU - Ferris, Robert L.

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