p53, which is over-expressed in many malignancies, is an attractive target for cancer immunotherapy. To enhance p53 specific immunity in a human p53 tolerant (Hupki) mouse model, we employed a chemo-immunotherapy strategy with Sunitinib and an MVA vaccine expressing p53 as a tumor antigen (MVAp53). Mice bearing 4T1-p53 tumors, a mouse mammary carcinoma transfected with human p53, exhibited splenomegaly with increased numbers of myeloid derived suppressor cells (MDSC). To reduce MDSC populations, 4T1-p53 tumor bearing mice were treated with the multi-targeted receptor tyrosine kinase inhibitor, Sunitinib. Mice were also immunized with MVAp53. Compared to mice treated with Sunitinib or MVAp53 alone, the combination resulted in enhanced rejection of established 4T1-p53 tumors. Mice rejecting 4T1-p53 tumors developed tumor specific immunity and rejected a subsequent challenge with the same tumor at 60 days. Analysis of splenocytes from sunitinib treated mice revealed reduced numbers of CD11b+Gr-1+ MDSC and reduced numbers of CD4+CD25+ T cells. Sunitinib treatment, when administered with MVAp53, enhanced p53 specific IFN-\#947; secretion from both CD8+ and CD4+ T cells. These data demonstrated that the combination of Sunitinib with MVAp53 vaccination results in synergistic effects in the rejection of established tumors. This chemo-immunotherapy approach holds potential for patients with p53 expressing malignancy.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 362.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009