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CTLA-4 blockade enhances effect of poxvirus vaccine targeting p53 in tumor model.
2003 MAY 7 - (NewsRx.com & NewsRx.net) -- A CTLA-4 blockade enhanced the therapeutic effect of an attenuated poxvirus vaccine targeting p53 in an established murine tumor model.
"p53 is overexpressed by half of all cancers, and is an attractive target for a vaccine approach to immunotherapy. p53 overexpression is frequently the result of point mutations, which leaves the majority of the protein in its wild-type form. Therefore, the majority of p53 sequence is wild type, making it a self-protein for which tolerance plays a role in limiting immune responses," scientists in the United States report.
"To overcome tolerance to p53, we have expressed wild-type murine p53 in the nonpathogenic attenuated poxvirus, modified vaccinia virus Ankara [recombinant modified vaccinia virus Ankara expressing wild-type murine p53 (rMVAp53)]," stated Jonathan Espenschied and colleagues at the City of Hope National Medical Center in Duarte, California.
They continued, "Mice immunized with rMVAp53 vaccine developed vigorous p53-specific CTL responses. rMVAp53 vaccine was evaluated for its ability to inhibit the outgrowth of the syngeneic murine sarcoma Meth A, which overexpresses mutant p53. Mice were inoculated with a lethal dose (5 x 10[superscript]5 cells injected s.c.) of Meth A tumor cells and vaccinated by i.p. injection 3 days later with 5 x 10[superscript]7 PFU of rMVAp53. The majority of mice remained tumor-free and resistant to rechallenge with Meth A tumor cells."
"We wished to determine whether ...
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Source: HighBeam Research, CTLA-4 blockade enhances effect of poxvirus vaccine targeting p53 in...