Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine

e13050 Background: To develop therapeutic cancer vaccine, we conducted a phase II study of personalized peptide vaccine (PPV) for refractory breast cancer patients. Methods: Thirty-four refractory breast cancer patients, including 8 triple negative (TN) cases, were enrolled to this study. A maximum of four HLA-class IA (A2, A3s, A24, A26)-matched peptides showing higher antigen-specific IgG responses were administered. Inflammatory markers, cytokines, and peptide-specific CTL and IgG responses were examined before and after vaccination to identify prognostic factors for overall survival (OS). Results: No vaccine-related severe adverse events were observed. Median numbers of preceding chemo- and/or hormone therapy regimens and median treatment duration from the recurrence to the vaccination were 2 regimens and 37 months, respectively. Three patients did not complete the 6th vaccination because of rapid disease progression. CTL or IgG boosting by PPV was observed in 16 or 18 of 31 patients at the time of 6th vaccination. IgG boosting was observed in all 24 patients tested at 12th vaccination. Median survival time of 31 patients receiving > 6th vaccination after the vaccination was 474 days with 2 complete responses and 1 partial response. There were no significant differences between 8 TN cases and the other cases from points of immunological and clinical responses. Lymphocyte frequency (Hazard ratio of 0.906, p=0.019) well associated with OS by multivariate Cox proportional hazard regression analysis for pre-vaccination samples. Conclusions: Next steps of PPV for the refractory breast cancer patients were warranted because of the lower toxicity and favorite immune responses along with possible clinical benefits.

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Effect of immunization with Ii-key modified HER2 (776-790) peptide vaccine (AE37) on immunologic responses in prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e16037 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e16037-e16037

Author(s):

Sonia A. Perez ◽

Eleftheria Anastasopoulou ◽

Efi Pappou ◽

Panagiotis Tzonis ◽

Stratos Bisias ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Peptide Vaccine ◽

Treg Cells ◽

Vaccine Responses ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Proliferation Assays

e16037 Background: We have shown that the AE37 vaccine (Ii-Key modified HER2(776-790) peptide) is safe and induces HER2/neu–specific cellular immune responses in patients with prostate cancer (Perez SA et al Clin. Cancer Res. 2010, 16:3495). We now present data from 4-year immunological assessments of prostate cancer patients who received AE37. Methods: Seventeen patients in a phase I study were given 6 doses of AE37 at monthly intervals and one additional dose a year after initiating treatment. Immunological testing to assess active versus suppressive immunity was conducted one month (intermediate-term immunomonitoring [ITI]) and 3 years (long-term immunomonitoring [LTI]) after the final dose of AE37. ELISPOT and proliferation assays were conducted to assess cytokine secretion and mitogenic response to antigen. DTH reactions were measured to assess in vivo immune response to antigen. All assays were conducted using native HER2(776-790) peptide (AE36). The percent Treg cells and ng/ml TGFβ were determined as markers for immune suppression. Results: Neither ELISPOT nor proliferation assays were statistically different at LTI compared to ITI. While clearly above pre-vaccine responses, the drop in DTH was statistically significant (p < 0.05). Similarly, the increase in Treg cells and circulating TGFβ was also statistically significant. An increase of >200 % in PSA-doubling time at any point during the study was observed in 6/17 patients, with 3 retaining this effect to 5 years. Conclusions: AE37 generates immunological memory associated with possible clinical efficacy in spite of Tregs and TGF-β levels returning at 4 years after being decreased for up to 6 months after initial AE37 vaccination. These results support further randomized testing of the AE37 vaccine. Clinical trial information: 2006-003299-37. [Table: see text]

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Identification of Peptide Vaccine Candidates for Prostate Cancer Patients with HLA-A3 Supertype Alleles

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-05-0682 ◽

2005 ◽

Vol 11 (19) ◽

pp. 6933-6943 ◽

Cited By ~ 28

Author(s):

Satoko Matsueda ◽

Hiroko Takedatsu ◽

Akihisa Yao ◽

Masahiro Tanaka ◽

Masanori Noguchi ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Peptide Vaccine ◽

Vaccine Candidates

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Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients

Cancer Immunology Immunotherapy ◽

10.1007/s00262-015-1756-7 ◽

2015 ◽

Vol 64 (12) ◽

pp. 1565-1573 ◽

Cited By ~ 2

Author(s):

Hiromitsu Araki ◽

Xiaoliang Pang ◽

Nobukazu Komatsu ◽

Mikiko Soejima ◽

Nawoe Miyata ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Vaccine Efficacy ◽

Prognostic Biomarker ◽

Peptide Vaccine ◽

Promoter Polymorphism ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer

Cancer Immunology Immunotherapy ◽

10.1007/s00262-010-0822-4 ◽

2010 ◽

Vol 59 (7) ◽

pp. 1001-1009 ◽

Cited By ~ 78

Author(s):

Masanori Noguchi ◽

Tatsuyuki Kakuma ◽

Hirotsugu Uemura ◽

Yasutomo Nasu ◽

Hiromi Kumon ◽

...

Keyword(s):

Prostate Cancer ◽

Low Dose ◽

Phase Ii Trial ◽

Standard Dose ◽

Peptide Vaccine ◽

Estramustine Phosphate ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Randomized Phase Ii ◽

Personalized Peptide Vaccine

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Personalized peptide vaccine in prostate cancer: capitalizing on existing immunity

Translational Cancer Research ◽

10.21037/tcr.2016.12.27 ◽

2016 ◽

Vol 5 (S7) ◽

pp. S1333-S1335

Author(s):

Ravi A. Madan ◽

James L. Gulley

Keyword(s):

Prostate Cancer ◽

Peptide Vaccine ◽

Personalized Peptide Vaccine

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Effect of immunization with the ii-key modified HER2/neu(776-790) (AE37) peptide vaccine on pre-existent immunity to PSA in HLA-A24+ prostate cancer patients: Association with increased AE37-specific immunologic responses.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15125 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15125-e15125

Author(s):

Sonia A. Perez ◽

Eleftheria Anastasopoulou ◽

Efi Pappou ◽

Nikolaos Fragkiskos Pistamaltzian ◽

Eric von Hofe ◽

...

Keyword(s):

Prostate Cancer ◽

T Cells ◽

Phase I ◽

Cancer Patients ◽

Phase I Study ◽

Peptide Vaccine ◽

Therapeutic Vaccine ◽

Immunological Responses ◽

Her 2 ◽

Mhc Alleles

e15125 Background: In solid tumors such as prostate cancer, novel biomarkers are needed for assessing immunological responses and clinical efficacy. By using dextramers specific for PSA we have retrospectively analyzed CD8+ T cell frequencies in patients with HER-2/neu+ prostate cancer who had received the AE37 vaccine in a phase I study (Perez SA et al Clin. Cancer Res. 2010, 16:3495). AE37 binds to numerous MHC alleles (Perez SA et al Clin. Cancer Res. 2010, 16:3495) (Salazar LG, Clin Cancer Res. 2003, 9:5559) encouraging its use as a therapeutic vaccine for general HER-2/neu+ cancer patients. Methods: CD8+ Dextramer+ T cells were measured, retrospectively, in the blood (which was stored in N2 liquid) of HLA-A24+ (n= 12) and HLA-A2+ (n=12) patients. Blood lymphocytes collected before, during and 6-months post vaccination were all analyzed with the same method involving direct labeling with HLA A24/PSA(153-161)-FITC and PerCP-conjugated anti-CD8 monoclonal antibody. Results: 8 of 12 HLA-A24+ patients had preexistent immunity to PSA as evidenced by the increased percentages of CD8+ HLA-A24/PSA(153-161)+ T cells in pre-vaccination samples. All of these patients had shown increased in vitro (IFNγ-based ELISPOT assay) and in vivo (DTH) immunological responses to the AE37 vaccine in the phase I study (Perez SA et al Clin. Cancer Res. 2010, 16:3495). Importantly, this preexistent immunity was significantly boosted in 5 patients during vaccinations with AE37, was slightly increased in 2 others, whereas in one patient no changes were observed during vaccinations. Conclusions: These results suggest that HLA-A24 expression along with preexistent immunity to PSA(153-164) may represent biomarkers based on which HER-2/neu+ patients can be selected most likely to benefit from vaccination with AE37. A phase II trial is warranted for validating these results. Given the promiscuity of AE37, it would be intriguing to examine if preexistent immunity to other prostate antigens restricted by various MHC alleles exist and to demonstrate an increase in preexistent immunity in association with a positive immunologic response to vaccination with AE37.

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