Systemic impact on tumor growth after combined immuno-thermal ablation in a murine model of colorectal cancer.

Abstract

198 Background: Cryoablation exposes tumoral antigens capable of provoking an anti-cancer immune response. The addition of immunotherapy alongside cryoablation may synergistically promote a more robust systemic response. The purpose of this investigation was to study the growth of targeted and off-target tumors after combined cryoablation and dual immune checkpoint blockade (DICB). Methods: Sixty BALB/c mice were implanted with bilateral flank injections of 0.5 x 106 CT26.WT colorectal cancer cells (CRL- 2638; ATCC, Manassas, VA). Tumor volume was measured every other day via caliper (LxW2). Mice were randomly assigned to receive either sham injections (InVivoMAb IgG controls), dual anti-PD-1 and anti-CTLA-4 (DICB) (Clone J43 & Clone 9D9; BioXcell, West Lebanon, NH, USA), or DICB plus either partial or full cryoablation of a single targeted tumor. Treatment day 0 began once tumors reached a volume of ~300mm3. Injections of antibodies were given on treatment day 0, 3, and 5. Cryoablation was performed on treatment day 2. Full ablation was achieved via two 3-minute cycles at 100% power and partial ablation was defined as a single 3 minute cycle at 70% power ablation (Visual-ICE System, Galil Medical, St. Paul MN). Animals were sacrificed at 7 and 14 days after treatment. Results: There was an average of 177.15% ± 75.22 (SD) increase in tumor volume among control animals and 14.47% ± 9.69 decrease in animals treated solely with DICB. Mice that received full ablation demonstrated an average 72.39% ± 29.21 decreased volume in the target tumors and 48.94% ± 25.97 decrease in the off-target tumors. Partially ablated mice averaged 81.21% ± 16.43 decreased volume in the target tumors and 35.87% ± 16.95 decreased volume in the off-target tumors. The mean change in volume of every group was significantly less than that of the control (p < 0.05) and there was a significantly larger reduction in volume between both the full and the partial target tumors versus the DICB group (p < 0.05). Conclusions: The addition of cryoablation to DICB resulted in a significant reduction in volume of the targeted tumors. Additionally, this combination led to larger volume reductions in off-target tumors as compared to immunotherapy alone.