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. Key words: peptide vaccination; pancreatic cancer; mutant ras; granulocyte-macrophage colony-stimulating factor; adenocarcinomaMost patients with pancreatic adenocarcinoma are inoperable at the time of diagnosis. There is currently no effective non-surgical treatment option, and median survival time remains short (3 to 4 months). The small subgroup of operable cases (approx. 10%) has a median survival time of approximately 18 months. 1 Advances in treatment options for patients with pancreatic cancer are urgently needed.Mutations in the proto-oncogenes of the RAS family are frequent in human malignancies, and K-RAS mutations are found in most adenocarcinomas of the pancreas. 2 In addition, the fact that most RAS mutations are confined to codons 12, 13 and 61 3 makes the protein an attractive target for induction of tumor-specific T cells. Previous studies have shown that immune responses to mutated ras peptides and proteins can occur spontaneously in patients with malignancy or can be elicited in normal individuals. 4 -10 Peptide-specific T-cell responsiveness against mutant ras can also be induced in vivo in cancer patients by vaccination with antigen-presenting cells (APCs) loaded ex vivo with ras peptides or ras peptides emulsified in adjuvant. 11,12 These peptides, which are 13 to 17 amino acids in length, represent natural ras epitopes [13][14][15] and are designed primarily to...

SummaryBackground Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the effi cacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24Gag , in adults infected with HIV-1.

HIV-associated specific responses were safely induced in most patients by Vacc-4x in a dose-dependent manner and were also influenced by the HLA haplotype.

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The atherogenic risk profile was improved with K85 in subjects with combined hyperlipidaemia, but n-3 fatty acids supplementation did not affect glucose/insulin homeostasis.