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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 OE, Herrin VE, Ibrahim RA, Toubaji A, Bernstein S, Dakheel O, Steinberg SM, Abu Eid R, Mkrtichyan M, Berzofsky JA, Khleif SN - J Transl Med (2014)

Bottom Line: HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro.There were no RECIST responses in any patient.The majority of toxicities were grade I and II.

View Article: PubMed Central - PubMed

Affiliation: Cancer Vaccine Branch, CCR, NCI, 10 Center Drive, Bethesda 20892, MD, USA. skhleif@gru.edu.

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.

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Related in: MedlinePlus

Progression free survival and overall survival for the full cohort. Progression free survival (A) and overall survival (B) for the full cohort. PFS was calculated as time from the date of consent until evidence of disease progression or last follow-up. OS was calculated as time from consent date until death or last follow-up.
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Fig3: Progression free survival and overall survival for the full cohort. Progression free survival (A) and overall survival (B) for the full cohort. PFS was calculated as time from the date of consent until evidence of disease progression or last follow-up. OS was calculated as time from consent date until death or last follow-up.

Mentions: Clinical response was evaluated in 29 out of the 32 treated patients (Tables 1 and 2). Three patients (2A, 9A and 6B) were excluded from the analysis since they received only one vaccine due to poor performance status. Out of the 29 evaluable patients the clinical outcome was as follows: Twenty five patients had progression of disease during the course of treatment (13/16 on arm A and 12/13 patients on arm B); one patient (5A) was taken off the study due to poor performance status after receiving 2 vaccine doses; one patient (#13B) decided to withdraw from the study and had a stable disease after receiving 6 vaccine doses; and the remaining 2 patients (#15A and 16A) completed the treatment without disease progression. Patient 15A was enrolled on the study with NED after being treated with 2 surgeries, 2 courses of radiation therapy and one chemotherapy regimen. This patient received a total of 10 vaccine doses and continued to have no evidence of disease as of the last follow up (67.1 months). Patient 16A was enrolled on the study with stage IV disease after being treated with radiation therapy and 2 courses of chemotherapy. This patient completed a total of 14 vaccine doses and continued to have a stable disease, as of the last available follow up (115.9 months). There were no RECIST responses in any patient. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively (Figure 3). Arm A had a median OS and PFS of 9.7 and 3.6 months, respectively, while patients on arm B had a median OS and PFS of 11.4 and 3.5 months, respectively. Eighteen patients received fewer than five vaccine doses and had a median OS and PFS of 7.2 and 1.7 months, respectively. On the other hand, 11 patients who were able to receive five or more vaccine doses had a median OS and PFS of 20.1 and 6.9 months, respectively. Patients who had an immune response had a median OS and PFS of 8.7and 5.3 months, respectively, while the non-immune responders had a median OS and PFS of 6.3 and 2.8 months, respectively.Figure 3


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 OE, Herrin VE, Ibrahim RA, Toubaji A, Bernstein S, Dakheel O, Steinberg SM, Abu Eid R, Mkrtichyan M, Berzofsky JA, Khleif SN - J Transl Med (2014)

Progression free survival and overall survival for the full cohort. Progression free survival (A) and overall survival (B) for the full cohort. PFS was calculated as time from the date of consent until evidence of disease progression or last follow-up. OS was calculated as time from consent date until death or last follow-up.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4269078&req=5

Fig3: Progression free survival and overall survival for the full cohort. Progression free survival (A) and overall survival (B) for the full cohort. PFS was calculated as time from the date of consent until evidence of disease progression or last follow-up. OS was calculated as time from consent date until death or last follow-up.
Mentions: Clinical response was evaluated in 29 out of the 32 treated patients (Tables 1 and 2). Three patients (2A, 9A and 6B) were excluded from the analysis since they received only one vaccine due to poor performance status. Out of the 29 evaluable patients the clinical outcome was as follows: Twenty five patients had progression of disease during the course of treatment (13/16 on arm A and 12/13 patients on arm B); one patient (5A) was taken off the study due to poor performance status after receiving 2 vaccine doses; one patient (#13B) decided to withdraw from the study and had a stable disease after receiving 6 vaccine doses; and the remaining 2 patients (#15A and 16A) completed the treatment without disease progression. Patient 15A was enrolled on the study with NED after being treated with 2 surgeries, 2 courses of radiation therapy and one chemotherapy regimen. This patient received a total of 10 vaccine doses and continued to have no evidence of disease as of the last follow up (67.1 months). Patient 16A was enrolled on the study with stage IV disease after being treated with radiation therapy and 2 courses of chemotherapy. This patient completed a total of 14 vaccine doses and continued to have a stable disease, as of the last available follow up (115.9 months). There were no RECIST responses in any patient. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively (Figure 3). Arm A had a median OS and PFS of 9.7 and 3.6 months, respectively, while patients on arm B had a median OS and PFS of 11.4 and 3.5 months, respectively. Eighteen patients received fewer than five vaccine doses and had a median OS and PFS of 7.2 and 1.7 months, respectively. On the other hand, 11 patients who were able to receive five or more vaccine doses had a median OS and PFS of 20.1 and 6.9 months, respectively. Patients who had an immune response had a median OS and PFS of 8.7and 5.3 months, respectively, while the non-immune responders had a median OS and PFS of 6.3 and 2.8 months, respectively.Figure 3

Bottom Line: HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro.There were no RECIST responses in any patient.The majority of toxicities were grade I and II.

View Article: PubMed Central - PubMed

Affiliation: Cancer Vaccine Branch, CCR, NCI, 10 Center Drive, Bethesda 20892, MD, USA. skhleif@gru.edu.

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.

Show MeSH
Related in: MedlinePlus