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

• Published in: International journal of cancer Vol. 92; no. 3; pp. 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: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01-05-2001; Wiley-Liss
• 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; Adenocarcinoma; Antineoplastic agent; Human; Drug combination; Immune response; Peptides; Cytokine; Vaccine; Malignant tumor; Treatment; Polypeptide; C-Onc gene; Immunotherapy; Digestive diseases; Genetics; Mutation; Pancreas; Granulocyte macrophage colony stimulating factor; Protooncogene; Pancreatic disease
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.1205

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.