Chapter 3 │ Page 97 kinetics per condition over time, data is represented as mean ± SD. (D) Kaplan-Meier survival plot per treatment condition during the predetermined duration of the study (100 days). (E) Forest plot indicating hazards ratios of the di erent treatment conditions compared to control mice that received untreated vaccines. (F) Mathematical overview of tumor development on rechallenge site and protection percentage per vaccination condition. Statistically significant hazard ratios (HR) are indicated (+). Statistical significance was determined with a Mixed Model ANOVA for the mean tumor kinetics, the Log-Rank (Mantel-Cox) test for mouse survival, and Cox Regression model to calculate hazard ratios and protection e ects. (* p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001). longer than those in the CDDPlow group (51 vs. 62 days, p = 0.0312), while COMBOhigh extended survival from 59 to 75 days compared to CDDPhigh (p = 0.0283). In addition to improved survival, Cox Regression analysis with hazard ratio calculations confirmed that treated vaccines provided a significant protective benefit against tumor development and subsequent death (Figure 11E). Lower hazard ratios, indicating a reduced risk of developing a lethal tumor, were observed for NTP, CDDPhigh and the positive control mitoxantrone. Strikingly, COMBOhigh exhibited again the lowest tumor risk, with a hazard ratio of only 0.08 compared to untreated vaccines (p < 0.0001). These trends were further reflected in the protection percentages calculated for each treatment condition (Figure 11F). All mice in the untreated and CDDPlow conditions developed a tumor, whereas one mouse in the NTP and mitoxantrone groups remained completely tumor-free. Most notably, COMBOhigh provided 37.5% protection, with only five out of eight mice developing tumors, underscoring its ability to elicit a potent and long-lasting immune-engaging anti-tumor response. Taken together, our findings highlighted the therapeutic potential of NTP in delaying tumor onset, reducing growth kinetics, and even improving survival through tumor protection in our HNSCC mouse model. This data underlines the ICD-inducing capacity of NTP and its potential to boost the immunogenicity of other therapies in a combinatorial setting, making it an appealing strategy for immune-based cancer therapy.
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