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

doi:10.1186/s12967-014-0353-4

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

Dental Education

National Cancer Institute (NCI), National Institutes of Health (NIH) - USA

Research output: Contribution to journal › Article › peer-review

25 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) (Arm A) 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 language	English
Pages (from-to)	1-10
Number of pages	10
Journal	Journal of translational medicine
Volume	12
Issue number	353
DOIs	https://doi.org/10.1186/s12967-014-0353-4
Publication status	Published - 16 Dec 2014

Bibliographical note

This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Keywords

Dendritic cells
HPV16
E6
E7
Vaccine
Cervical cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12967-014-0353-4Licence: CC BY

Rasha Abu Eid
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cancer Centre
- School of Medicine, Medical Sciences & Nutrition, Dental Education - Senior Lecturer
Person: Academic

Cite this

Rahma, O. E., Herrin, V. E., Ibrahim, R. A., Toubaji, A., Bernstein, S., Dakheel, O., Steinberg, S. M., Abu Eid, R., Mkrtichyan, M., Berzofsky, J. A., & Khleif, S. N. (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, 12(353), 1-10. https://doi.org/10.1186/s12967-014-0353-4

Rahma, OE, Herrin, VE, Ibrahim, RA, Toubaji, A, Bernstein, S, Dakheel, O, Steinberg, SM, Abu Eid, R, 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. 353, pp. 1-10. https://doi.org/10.1186/s12967-014-0353-4

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title = "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",

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) (Arm A) 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.",

keywords = "Dendritic cells, HPV16, E6, E7, Vaccine, Cervical cancer",

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

note = "This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.",

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day = "16",

doi = "10.1186/s12967-014-0353-4",

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TY - JOUR

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 - Abu Eid, Rasha

AU - Mkrtichyan, Mikayel

AU - Berzofsky, Jay A

AU - Khleif, Samir N

N1 - This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

PY - 2014/12/16

Y1 - 2014/12/16

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) (Arm A) 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) (Arm A) 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 - Dendritic cells

KW - HPV16

KW - E6

KW - E7

KW - Vaccine

KW - Cervical cancer

U2 - 10.1186/s12967-014-0353-4

DO - 10.1186/s12967-014-0353-4

M3 - Article

C2 - 25510844

VL - 12

SP - 1

EP - 10

JO - Journal of translational medicine

JF - Journal of translational medicine

IS - 353

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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Rasha Abu Eid

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