Induction of cellular immunity in chimpanzees to human tumor-associated antigen mucin by vaccination with MUC-1 cDNA-transfected Epstein-Barr virus-immortalized autologous B cells.

Abstract

(19,(25)(26)(27)(28)(29)(30). Studies performed to date with mucin-specific T-cell lines and clones have shown that CTLs recognize an immunodominant epitope formed at the junction of two tandem repeats, resulting from underglycosylation on tumor cells, and consisting of the amino acid sequence PDTRP. The same sequence is also recognized by several highly tumor-specific anti-mucin monoclonal antibodies (21-23) as well as some patients' sera (24). Depending on the inherited number of tandem repeats present in the mucin of different individuals, this epitope can be repeated 20-100 or more times per molecule. Moreover, the threedimensional structure of the repeat is very rigid with each epitope being not only a sequence repeat but also a threedimensional repeat (31,32). This unusual structure combined with the high epitope density appears to allow a crosslinking of the T-cell receptor and therefore a direct binding and major histocompatibility complex (MHC)-unrestricted recognition of the mucin molecule on tumor cells by specific CTLs (25)(26)(27)(28).We have recently determined that most human HLA alleles do not bind mucin peptides containing this amino acid sequence, and thus MHC-restricted recognition of this epitope does not

Production of High-Titer Epstein-Barr Virus Recombinants Derived from Akata Cells by Using a Bacterial Artificial Chromosome System

“…Experimental data described above clearly demonstrate that AK-BAC can be used as a replication-competent vector for expressing various transgenes in LCLs. As LCLs expressing transgenes can be used as antigen-presenting cells for immunotherapy (13,22), expediting the process of transgene insertion into the EBV genome is a matter of importance. Therefore, we generated a derivative of AK-BAC, to which any kind of cDNA cassette could be inserted by simple in vitro ligation.…”

The Cooperation between Two CD4 T Cells Induces Tumor Protective Immunity in MUC.1 Transgenic Mice

“…Despite the fact that CD8 T cell tolerance to MUC.1 has been broken in monkeys after DNA vaccination (17), and in MUC.1-Tg mice immunized with armed DC (18 -20), the induction of CD4 T cells specific for a MUC.1 peptide in MUC.1-Tg mice has not been shown previously.…”

Vaccine Development Against Novel Breast Cancer Antigens

“…The whole MUC1 protein has been delivered in a vaccinia construct [18,35], as a construct in DNA immunisation [36], in transfected dendritic cells [37] and in transfected EBV-B cells [38]. In none of these studies was the specificity of the CTL ascertained.…”