A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma.
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.
Maki
Robert G
RG
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021-6007, USA. makir@mskcc.org
Livingston
Philip O
PO
Lewis
Jonathan J
JJ
Janetzki
Sylvia
S
Klimstra
David
D
Desantis
Diann
D
Srivastava
Pramod K
PK
Brennan
Murray F
MF
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
D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; C484813:vitespin