DNA Immunization with Ras Oncogene Peptide Elicits T-Cell Responses.(Brief Article)

2001 FEB 14 - (NewsRx.com & NewsRx.net) --

- by Michelle Marble, staff medical writer -- Researchers in the United States have discovered a ras oncogene peptide with anticancer potential.

"Mutations in ras proto oncogenes are commonly found in a diversity of malignancies and may encode unique, non-self epitopes for T-cell-mediated antitumor activity," stated J.A. Bristol and colleagues, U.S. National Cancer Institute, Bethesda, Maryland. "In a BALB/c (H-2(d)) murine model, we have identified a single peptide sequence derived from the ras oncogenes that contained both CD8(+) and CD4(+) T-cell epitopes in a nested configuration."

Bristol et al. published the results of their study in the journal Cellular Immunology ("Identification of a ras oncogene peptide that contains both CD4(+) and CD8(+) T-cell epitopes in a nested configuration and elicits both T-cell subset responses by peptide or DNA immunization," Cell Immunol, 2000;205(2):73-83).

"This peptide reflected ras sequence 4-16, and contained the substitution of Gly to Val at position 12 [4-16(Val12)]," continued the researchers. "Mice immunized with this 13-mer peptide induced a strong antigen (Ag)-specific CD4(+) proliferative response in vitro."

In contrast, the researchers observed that mice inoculated with the wild-type ras sequence did not generate a peptide-specific T-cell response.

Mice immunized with the ras 4-16(Val12) peptide, on the other hand, concomitantly displayed an antigen (Ag)-specific CD8(+) cytotoxic T lymphocyte (CTL) response. This was determined through lysis of syngeneic tumor target cells that had been incubated with the nominal 9-mer nested epitope peptide [4-12(Val12)], as well as through lysis of tumor target cells expressing the corresponding ras codon 12 mutation.