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 language | English (US) |
|---|---|
| Pages (from-to) | 2433-2444 |
| Number of pages | 12 |
| Journal | Clinical Cancer Research |
| Volume | 20 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2014 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Phase i dendritic cell p53 peptide vaccine for head and neck cancer
AU - Schuler, Patrick J.
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.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84899728764&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899728764&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-13-2617
DO - 10.1158/1078-0432.CCR-13-2617
M3 - Article
C2 - 24583792
AN - SCOPUS:84899728764
VL - 20
SP - 2433
EP - 2444
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 9
ER -