Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer

Osama E. Rahma, Vincent E. Herrin, Rami A. Ibrahim, Anton Toubaji, Sarah Bernstein, Omar Dakheel, Seth M. Steinberg, Rasha Abu Eid, Mikayel Mkrtichyan, Jay A. Berzofsky, Samir N. Khleif

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Background: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. Methods: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18-26) (ArmA) or HPV16 E7 (12-20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as "Pre-Immature Dentritic Cells". Results: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. Conclusions: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18-26) or HPV16 E7 (12-20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations.

Original languageEnglish (US)
Article number353
JournalJournal of Translational Medicine
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2014

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Uterine Cervical Neoplasms
Dendritic Cells
Peptides
Enzyme-Linked Immunospot Assay
Active Immunotherapy
Human papillomavirus 18
Oncogenic Viruses
Human papillomavirus 16
Granulocyte-Macrophage Colony-Stimulating Factor
Disease-Free Survival
Viruses
Toxicity
Assays
Vaccines
Genes
Survival
Proteins

Keywords

  • Cervical cancer
  • Dendritic cells
  • E6
  • E7
  • HPV16
  • Vaccine

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer. / Rahma, Osama E.; Herrin, Vincent E.; Ibrahim, Rami A.; Toubaji, Anton; Bernstein, Sarah; Dakheel, Omar; Steinberg, Seth M.; Eid, Rasha Abu; Mkrtichyan, Mikayel; Berzofsky, Jay A.; Khleif, Samir N.

In: Journal of Translational Medicine, Vol. 12, No. 1, 353, 01.01.2014.

Research output: Contribution to journalReview article

Rahma, OE, Herrin, VE, Ibrahim, RA, Toubaji, A, Bernstein, S, Dakheel, O, Steinberg, SM, Eid, RA, Mkrtichyan, M, Berzofsky, JA & Khleif, SN 2014, 'Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer', Journal of Translational Medicine, vol. 12, no. 1, 353. https://doi.org/10.1186/s12967-014-0353-4
Rahma, Osama E. ; Herrin, Vincent E. ; Ibrahim, Rami A. ; Toubaji, Anton ; Bernstein, Sarah ; Dakheel, Omar ; Steinberg, Seth M. ; Eid, Rasha Abu ; Mkrtichyan, Mikayel ; Berzofsky, Jay A. ; Khleif, Samir N. / Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer. In: Journal of Translational Medicine. 2014 ; Vol. 12, No. 1.
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abstract = "Background: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. Methods: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18-26) (ArmA) or HPV16 E7 (12-20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as {"}Pre-Immature Dentritic Cells{"}. Results: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63{\%}) evaluable patients in arm A and 7/12 (58{\%}) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. Conclusions: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18-26) or HPV16 E7 (12-20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations.",
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T1 - Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer

AU - Rahma, Osama E.

AU - Herrin, Vincent E.

AU - Ibrahim, Rami A.

AU - Toubaji, Anton

AU - Bernstein, Sarah

AU - Dakheel, Omar

AU - Steinberg, Seth M.

AU - Eid, Rasha Abu

AU - Mkrtichyan, Mikayel

AU - Berzofsky, Jay A.

AU - Khleif, Samir N.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. Methods: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18-26) (ArmA) or HPV16 E7 (12-20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as "Pre-Immature Dentritic Cells". Results: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. Conclusions: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18-26) or HPV16 E7 (12-20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations.

AB - Background: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. Methods: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18-26) (ArmA) or HPV16 E7 (12-20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as "Pre-Immature Dentritic Cells". Results: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. Conclusions: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18-26) or HPV16 E7 (12-20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations.

KW - Cervical cancer

KW - Dendritic cells

KW - E6

KW - E7

KW - HPV16

KW - Vaccine

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DO - 10.1186/s12967-014-0353-4

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