This work demonstrates that common shared mutated epitopes such as those found in p53 can elicit immunogenic responses and that the application of ACT may be extended to patients with any cancer histology that expresses both HLA-A*0201 and the p53 p.R175H mutation.
One particular mutant, R175H, is a structural mutant that inactivates the DNA damage response pathway and acquires oncogenic functions that promotes both cancer and drug resistance.
Here, we developed a genetically modified porcine model of cancer in which animals express a mutation in TP53 (which encodes p53) that is orthologous to one commonly found in humans (R175H in people, R167H in pigs).
We used the humanized p53 cancer mutant knock-in (R175H) mice and mouse mammary tumor virus (MMTV)-Wnt-1 transgenic (mWnt-1) mice to specifically address the gain of function of R175H in promoting breast cancer.
The contribution of PML to mutant p53 driven cancer was evaluated in a mouse model harboring a p53 mutation (p53 (wild-type/R172H) ) that recapitulates a frequent p53 mutation (p53 (R175H) ) in human sporadic and Li-Fraumeni cancers.