Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras.
K-ras mutations are frequently found in adenocarcinomas of the pancreas and can elicit mutation-specific immune responses. Targeting the immune system against mutant Ras may thus influence the clinical course of the disease. Twenty-three patients who were vaccinated after surgical resection for pancreatic adenocarcinoma (22 pancreaticoduodenectomies, one distal resection), in two previous Phase I/II clinical trials, were followed for more than 10 years with respect to long-term immunological T-cell reactivity and survival. The vaccine was composed of long synthetic mutant ras peptides designed mainly to elicit T-helper responses. Seventeen of 20 evaluable patients (85%) responded immunologically to the vaccine. Median survival for all patients was 27.5 months and 28 months for immune responders. The 5-year survival was 22% and 29%, respectively. Strikingly, 10-year survival was 20% (four patients out of 20 evaluable) versus zero (0/87) in a cohort of nonvaccinated patient treated in the same period. Three patients mounted a memory response up to 9 years after vaccination. The present observation of long-term immune response together with 10-year survival following surgical resection indicates that K-ras vaccination may consolidate the effect of surgery and represent an adjuvant treatment option for the future.
Wedén
Synne
S
Faculty of Medicine, University of Oslo.
Klemp
Marianne
M
Gladhaug
Ivar P
IP
Møller
Mona
M
Eriksen
Jon Amund
JA
Gaudernack
Gustav
G
Buanes
Trond
T
D000230:Adenocarcinoma / Q000276:immunology* / Q000601:surgery / Q000628:therapy; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000601:surgery / Q000628:therapy; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines