Dendritic cell vaccine boosts T cell-mediated immunity to tyrosinase.

2004 NOV 3 - (NewsRx.com & NewsRx.net) -- Vaccinia virus-transduced, CD34+-derived dendritic cell vaccination boosted T cell-mediated immunity to tyrosinase.

Six American Joint Committee on Cancer stage IV melanoma patients were enrolled into a Phase I study of vaccination with autologous CD34(+)-derived dendritic cells transduced with a modified vaccinia Ankara virus encoding human tyrosinase gene (MVA-hTyr). Patients received a first intravenous injection of 1 x 10[superscript]8 MVA-hTyr-transduced dendritic cells, followed by three s.c. injections at a 14-day interval. Treatment was well tolerated, except for low-grade fever (three of six patients), mild erythema at injection site (five of six), and vitiligo (two of six)," scientists writing in the journal Clinical Cancer Research report.

"A partial response, involving shrinkage of an s.c. nodule, later surgically removed, was observed in one patient, who then remained disease-free (>850 days)," said Massimo Di Nicola and colleagues at the Istituto Nazionale Tumori. "By human lymphocyte antigen tetramer analysis, significant and often long-lasting increases in frequency of T cells directed to tyrosinase[subscript]368-376 but not to gp100[subscript]209-217 were documented in periphery of four of five HLA-A*0201+ patients, a few days after vaccine administration."

"In addition, maturation phenotype of tyrosinase-specific T cell shifted toward the T effector memory/T terminally differentiate stages (CCR7-CD45RA[superscript]-/+) in synchrony with the T-cell frequency peaks," reported the researchers. "By enzyme-linked immunospot in peripheral blood of five HLA-A*0201+ ...