title: AE37 peptide vaccination in prostate cancer: identification of biomarkers in the context of prognosis and prediction.
abstract: A fundamental challenge in administering immunotherapies for cancer is the establishment of biomarkers that can predict patients' responsiveness to treatment. In this study, our aim was to predict the immunologic and clinical responses of vaccination therapy with an Ii-key-modified HER-2/neu peptide (Ii-key/HER-2(776-790) or AE37), applied in our recent phase I study in patients with prostate cancer. To this end, we retrospectively analyzed our data derived from immunologic determinations before, during and after primary series of vaccinations with AE37, as well as after one AE37 booster injection. Using the obtained data, we then observed the relationship between the immunologic parameters and clinical outcome of patients. We found that preexisting levels of transforming growth factor beta (TGF-β) had an inverse correlation with in vivo and in vitro immunologic responses to the AE37 vaccine which were measured as delayed-type hypersensitivity (DTH) and interferon gamma (IFN-γ) production in response to the native HER-2(776-790) (or AE36) peptide, respectively. Patients with preexistent IFN-γ immunity to AE36 developed positive DTH reactions after primary vaccinations and booster. Moreover, we could detect a direct correlation between IFN-γ production and DTH reactions in response to AE36 challenge in our vaccinated patients. DTH reactions were a stronger indicator for patients' overall survival (OS) than preexistent or vaccine-induced IFN-γ immunity. In contrast, we found that preexisting TGF-β levels were correlated with shorter patients' OS. These retrospective analyses suggest that the above biomarkers at the time-points measured offer promise for evaluating immunologic and clinical responses to AE37-based vaccinations.
authors: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 171 Alexandras Avenue, Athens, 11522, Greece.
authors: Sonia A
authors: SA
authors: Perez
authors: Eleftheria A
authors: EA
authors: Anastasopoulou
authors: Michael
authors: M
authors: Papamichail
authors: Constantin N
authors: CN
authors: Baxevanis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012107:Research Design; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta; C530655:AE37 vaccine; C573415:IFNG protein, human; C508053:ERBB2 protein, human