ISOLATION OF TYROSINASE-SPECIFIC CD8(-CELL CLONES FROM THE PERIPHERAL-BLOOD OF MELANOMA PATIENTS FOLLOWING IN-VITRO STIMULATION WITH RECOMBINANT VACCINIA VIRUS() AND CD4(+) T)

Citation
C. Yee et al., ISOLATION OF TYROSINASE-SPECIFIC CD8(-CELL CLONES FROM THE PERIPHERAL-BLOOD OF MELANOMA PATIENTS FOLLOWING IN-VITRO STIMULATION WITH RECOMBINANT VACCINIA VIRUS() AND CD4(+) T), The Journal of immunology, 157(9), 1996, pp. 4079-4086
Citations number
41
Categorie Soggetti
Immunology
Journal title
The Journal of immunology
ISSN journal
00221767 → ACNP
Volume
157
Issue
9
Year of publication
1996
Pages
4079 - 4086
Database
ISI
SICI code
0022-1767(1996)157:9<4079:IOTCCF>2.0.ZU;2-N
Abstract
The identification of Ags expressed by tumor cells and recognized by a utologous T cells has led to the prospect of treating cancer by adopti ve transfer of tumor-reactive T cells selected for Ag specificity, Tyr osinase is an Ag expressed by normal melanocytes as well as melanoma c ells for which responses by autologous T cells have been detected, To evaluate the frequency with which tyrosinase-specific T cells can be i solated from melanoma patients for potential use in therapy, a recombi nant vaccinia virus expressing tyrosinase was constructed for infectio n of autologous APCs that could be used to stimulate T cells reactive with this protein, Eight patients were studied, with peripheral blood serving as the source of both responder T cells and autologous APCs. T yrosinase-specific CD8(+) CTL clones were isolated from five of the ei ght patients with melanoma, The tyrosinase-specific CTL generated in t his manner recognized autologous tumor cells as well as targets expres sing the recombinant virus vector, CTL clones from three of the indivi duals were restricted to HLA-A28, -B8, and -B60, which have not previo usly been identified as alleles that can present immunogenic tyrosinas e peptides, Tyrosinase-specific CD4(+) T cell clones were isolated fro m six of the eight patients by stimulation with autologous APCs infect ed with recombinant vaccinia virus, and all these CD4(+) clones were c apable of recognizing autologous tumor cells, These studies demonstrat e a high prevalence of CD4(+) and CD8(+) tyrosinase-specific responses in peripheral blood and support the feasibility of using peripheral b lood to generate T cells for tumor therapy without the requirement for isolating T cells that have infiltrated tumor sites.