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Titolo:
Successful induction of immune responses against mutant ras in melanoma patients using intradermal injection of peptides and GM-CSF as adjuvant
Autore:
Hunger, RE; Brand, CU; Streit, M; Eriksen, JA; Gjertsen, MK; Saeterdal, I; Braathen, LR; Gaudernack, G;
Indirizzi:
Univ Bern, Inselpital, Dermatol Clin, CH-3012 Bern, Switzerland Univ BernBern Switzerland CH-3012 matol Clin, CH-3012 Bern, Switzerland Norwegian Radium Hosp, Dept Immunol, Sect Immunotherapy, Oslo, Norway Norwegian Radium Hosp Oslo Norway nol, Sect Immunotherapy, Oslo, Norway Norsk Hydro AS, Res Ctr, N-3901 Porsgrunn, Norway Norsk Hydro AS Porsgrunn Norway N-3901 Res Ctr, N-3901 Porsgrunn, Norway
Titolo Testata:
EXPERIMENTAL DERMATOLOGY
fascicolo: 3, volume: 10, anno: 2001,
pagine: 161 - 167
SICI:
0906-6705(200106)10:3<161:SIOIRA>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
PANCREATIC-CARCINOMA PATIENTS; COLONY-STIMULATING FACTOR; T-CELL RESPONSES; P21 RAS; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; POINT MUTATIONS; DENDRITIC CELLS; VACCINATION; GENERATION;
Keywords:
cancer vaccines; active immunotherapy; ras peptides; melanoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Hunger, RE Univ Bern, Inselpital, Dermatol Clin, CH-3012 Bern, SwitzerlandUniv Bern Bern Switzerland CH-3012 CH-3012 Bern, Switzerland
Citazione:
R.E. Hunger et al., "Successful induction of immune responses against mutant ras in melanoma patients using intradermal injection of peptides and GM-CSF as adjuvant", EXP DERMATO, 10(3), 2001, pp. 161-167

Abstract

The rapidly increasing incidence and mortality rate of malignant melanoma,together with the lack of efficient treatment of the late stages, makes ita serious threat to public health. Innovative new treatments are needed. The proteins of the vas-family of proto-oncogenes, functioning as relay switches for signalling pathways between cell surface and nucleus, are involvedin cell proliferation, differentiation, apoptosis and transformation. If over-expressed or mutated they can induce and/or maintain a transformed state of a cell. Codon 61 mutations of N-ras seem to be involved in melanoma development on sun exposed sites, In order to induce an immune response towards mutated N-ras proteins we performed a phase 1 feasibility study. Ten melanoma patients were immunized intradermally 6 times with N-ras peptides (residue 49-73) with 4 codon 61 mutations using GM-CSF as adjuvant. HLA typingwas not used as an inclusion criterion. Eight patients responded with strong delayed type hypersensitivity reactions. In 2 of the patients an in vitro response to the vaccine could also be detected. The specificity of the reaction could be confirmed by cloning of peptide-specific CD4 positive T cells from peripheral blood of the patients. Intradermal injection of vas peptides using GM-CSF as adjuvant is simple to perform and seems to be efficient in inducing cellular immune responses. Since a majority of the patients showed positive skin reactions and 2 of the patients analysed showed a T-helper response to this melanoma specific antigen, these promiscuous HLA classII binding mutant ras peptides may be candidates for inclusion into vaccine cocktails containing various established CTL epitopes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 13:20:49