AE37 peptide vaccination in prostate cancer: a 4-year immunological assessment updates on a phase I trial.
In our recent phase I trial, we demonstrated that the AE37 vaccine is safe and induces HER-2/neu-specific immunity in a heterogeneous population of HER-2/neu (+) prostate cancer patients. Herein, we tested whether one AE37 boost can induce long-lasting immunological memory in these patients. Twenty-three patients from the phase I study received one AE37 boost 6-month post-primary vaccinations. Local/systemic toxicities were evaluated following the booster injection. Immunological responses were monitored 1-month (long-term booster; LTB) and 3-year (long-term immunity; LTI) post-booster by delayed-type hypersensitivity, IFN-γ ELISPOT and proliferation assays. Regulatory T cell (Treg) frequencies, plasma transforming growth factor-β (TGF-β) and indoleamine 2,3-deoxygenase (IDO) activity levels were also determined at the same time points. The AE37 booster was safe and well tolerated. Immunological monitoring revealed vaccine-specific long-term immunity in most of the evaluated patients during both LTB and LTI, although individual levels of immunity during LTI were decreased compared with those measured 3 years earlier during LTB. This was paralleled with increased Tregs, TGF-β levels and IDO activity. One AE37 booster generated long-term immunological memory in HER-2/neu (+) prostate cancer patients, which was detectable 3 years later, albeit with a tendency to decline. Boosted patients had favorable clinical outcome in terms of overall and/or metastasis-free survival compared with historical groups with similar clinical characteristics at diagnosis. We suggest that more boosters and/or concomitant disarming of suppressor circuits may be necessary to sustain immunological memory, and therefore, further studies to optimize the AE37 booster schedule are warranted.
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Building No. 2, 3rd Floor, 171 Alexandras Avenue, 11522, Athens, Greece, perez@ciic.gr.
Sonia A
SA
Perez
Eleftheria A
EA
Anastasopoulou
Panagiotis
P
Tzonis
Cécile
C
Gouttefangeas
Hubert
H
Kalbacher
Michail
M
Papamichail
Constantin N
CN
Baxevanis
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000276:immunology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; C530655:AE37 vaccine; C508053:ERBB2 protein, human