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)
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
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.