title: A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma.
abstract: We performed a phase I pilot study to determine if autologous vaccine HSPPC-96 (gp96, Oncophage) could be purified from completely resected pancreas adenocarcinomas, to determine patient tolerance of vaccine and to explore immune responses and clinical outcomes of these patients. Subjects were vaccinated with 5 microg of autologous HSPPC-96 weekly for 4 doses. Serial ELISPOT assays of T cells for antitumor reactivity were performed. Subjects received neither adjuvant chemotherapy nor radiation. Ten patients received a full course of vaccinations. No dose-limiting toxicities were encountered. Immediate freezing in liquid nitrogen of the tumor specimen resulted in improved vaccine yield. Median overall survival is 2.2 years (Kaplan-Meier estimate). Autologous anti-HSPPC-96 ELISPOT reactivity increased significantly in 1 of 5 patients examined and a second had an increase of unclear significance. Three of 10 treated patients are alive without disease at 2.6, 2.7, and 5.0 years follow-up. There was no observed correlation between immune response and prognosis. This study demonstrates the feasibility of preparing HSPPC-96 from pancreatic adenocarcinomas. Examination of this novel approach using multiple dose levels is 1 approach to further investigate the immunogenicity and clinical utility of HSPPC-96 vaccination in this setting.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021-6007, USA. makir@mskcc.org
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
authors.forename: Philip O
authors.initials: PO
authors.lastname: Livingston
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Lewis
authors.forename: Sylvia
authors.initials: S
authors.lastname: Janetzki
authors.forename: David
authors.initials: D
authors.lastname: Klimstra
authors.forename: Diann
authors.initials: D
authors.lastname: Desantis
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Srivastava
authors.forename: Murray F
authors.initials: MF
authors.lastname: Brennan
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006360:Heat-Shock Proteins / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D007108:Immune Tolerance; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000601:surgery / Q000628:therapy*; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; C484813:vitespin