title: Cellular immunotherapy study of prostate cancer patients and resulting IgG responses to peptide epitopes predicted from prostate tumor-associated autoantigens.
abstract: The immunogenicity of a cellular immunotherapy using genetically modified vaccines to express α(1,3)galactosyl epitopes (αGal) was evaluated in advanced prostate cancer (PC) patients. In this dose escalation phase I study, we report safety, feasibility, and immunologic data of an immunotherapy composed of 2 human PC cell lines engineered to express αGal epitopes (HyperAcute-Prostate, HAP, NewLink Genetics). Eight patients received up to 12 biweekly vaccinations with HAP. Enrolled patients (aged range, 53-85 y) had American Joint Committee on Cancer stage IV, any T, any N, M1, Eastern Cooperative Oncology Group PS≤2, at least 1 prior hormonal treatment and <3 prior chemotherapies, adequate bone marrow and organ function, and albumin ≥3.0 g/dL. Serum IgG antibodies to synthetic peptides overexpressed in PC were determined by enzyme-linked immunosorbent assay. Results indicate that HAP immunotherapy induced humoral immune responses to autoantigens in 2 of 8 patients. These patients developed IgG antibody to multiple epitopes overexpressed in PC after immunization. These responding patients received higher doses of the immunotherapy suggesting a dose response. Two immunogenic proteins (prostate-specific membrane antigen, hepsin) belong to the extracellular molecules family participating in malignant cell invasion. Median overall survival for patients was 25.1 months with 1 patient surviving over 70 months with stable PSA and bone metastasis before expiring of other causes. Three of 8 patients showed PSA stabilization (>100 d). In conclusion, HAP immunotherapy induces IgG responses to epitopes from autoantigens overexpressed in PC suggesting dose-dependent effect. HAP represents a viable immunotherapy approach to induce immune responses against tumor cells and may provide clinical benefit with minimal toxicity.
authors.affiliation: Department of Urology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: George P
authors.initials: GP
authors.lastname: Hemstreet
authors.forename: Gabriela R
authors.initials: GR
authors.lastname: Rossi
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Pisarev
authors.forename: Charles A
authors.initials: CA
authors.lastname: Enke
authors.forename: Laura
authors.initials: L
authors.lastname: Helfner
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Hauke
authors.forename: Lucinda
authors.initials: L
authors.lastname: Tennant
authors.forename: William Jay
authors.initials: WJ
authors.lastname: Ramsey
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Vahanian
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Link
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D014312:Trisaccharides / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D010455:Peptides; D014312:Trisaccharides; C076569:alpha-galactosyl epitope