Abstract 2693: Amplification of tumor immunity with cryoablation

Abstract

Abstract Tumor cryoablation, the use of freezing temperatures to destroy tumor tissue while preserving tumor-associated antigens, has the potential to initiate or amplify tumor immunity. However, enhanced tumor immunity is not consistently observed in treated patients, suggesting inadequate immune priming by cryoablation itself. We hypothesize that cryoablation in coordination with DNA vaccination and/or immune modulation will amplify effector mechanisms to provide long-term anti-tumor protection. BALB/c mice implanted with a neu expressing mammary tumor TUBO received two electro-vaccinations 10 days apart, with neu DNA or blank vector, followed 4 days later with cryoablation or sham surgery of the tumor. Mice receiving both neu vaccination and cryoablation produced a 3-fold higher anti-neu antibody titer over neu vaccination alone (P<0.02) and a 16-fold higher titer over cryoablation alone (P<0.003). Combination treatment also provided full protection against TUBO re-challenge, supporting enhanced immunity by cryoablation. To test the effect of combining cryoablation with the depletion of regulatory T cells (Treg), 12 week old BALB Neu transgenic mice which had spontaneously developed ductal carcinoma in situ in the mammary glands were treated with α-CD25 mAb to deplete Tregs, partial cryoablation of the 4th mammary gland, or a combination of both. Development of palpable mammary tumor throughout all ten mammary glands was significantly delayed in mice receiving combination treatment over either treatment alone, indicating amplification of tumor immunity in Treg depleted mice by cryoablation. The mechanisms of amplified immunity are being investigated by analyzing a panel of inflammatory cytokines in the serum as well as gene expression in lymphocytes in the tumor, spleen, and tumor draining lymph nodes at different points after cryoablation. Phenotyping of tumor infiltrating immune cells post-cryoablation is also being assessed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2693. doi:10.1158/1538-7445.AM2011-2693