Intradermal ras peptide vaccination with granulocyte‐macrophage colony‐stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma

K‐RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancr...

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Bibliographic Details
Published in:International journal of cancer 2001-05, Vol.92 (3), p.441-450
Main Authors: Gjertsen, Marianne K., Buanes, Trond, Rosseland, Arne R., Bakka, Arne, Gladhaug, Ivar, Søreide, Odd, Eriksen, Jon A., Møller, Mona, Baksaas, Ingebjørg, Lothe, Ragnhild A., Sæterdal, Ingvil, Gaudernack, Gustav
Format: Article
Language:English
Subjects:
adenocarcinoma
Adenocarcinoma - immunology
Adenocarcinoma - mortality
Adenocarcinoma - prevention & control
Adjuvants, Immunologic - adverse effects
Adjuvants, Immunologic - therapeutic use
Adult
Aged
Aged, 80 and over
Antineoplastic agents
Biological and medical sciences
Female
Granulocyte-Macrophage Colony-Stimulating Factor - adverse effects
Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use
granulocyte‐macrophage colony‐stimulating factor
Humans
Hypersensitivity, Delayed - etiology
Immunotherapy
Injections, Intradermal
Lymphocytes, Tumor-Infiltrating - immunology
Male
Medical sciences
Middle Aged
mutant ras
pancreatic cancer
Pancreatic Neoplasms - immunology
Pancreatic Neoplasms - mortality
Pancreatic Neoplasms - prevention & control
peptide vaccination
Peptides - adverse effects
Peptides - therapeutic use
Pharmacology. Drug treatments
ras Proteins - adverse effects
ras Proteins - therapeutic use
Survival Rate
T-Lymphocytes - immunology
Treatment Outcome
Vaccination
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Summary:K‐RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte‐macrophage colony‐stimulating factor. Forty‐eight patients (10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide‐specific immunity was induced in 25 of 43 (58%) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end‐stage disease. Patients followed‐up for longer periods showed evidence of induction of long‐lived immunological memory against the ras mutations. CD4+ T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras‐specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients. Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non‐responders (median survival 148 days vs. 61 days, respectively; p = 0.0002). Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients. © 2001 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.1205