ADVANTAGES OF A NEW PARADIGM OF EXPERIMENTAL ONCOLOGY: INDIVIDUAL PROGNOSIS OF IMMUNOTHERAPY OUTCOME BASED ON SURROGATE MARKER ANALYSIS

Introduction. A novel 3S-paradigm of alternative experimental anti-cancer drug testing procedure was developed in parallel with a modern conception of personalized and predictive medicine to reveal both positive and negative effect in each experiment and topredict this effect individually. Breast cancer (BC) immunotherapy with interleukin-2 (IL-2) is a clear example of dual effect both in experimental research and BC clinics. Earlier, we showed that distinct changes in initial routine hematological parameters in intact mice can be concidered as surrogate markers for the negative effect of local IL-2 treatment in transplanted BC mouse model. The aim of the study.To show the advantage of the new paradigm: to reveal both beneficial and non-beneficial subgroups of IL-2 treated recipients, and to show the prognostic value of initial serum biochemical parameters associated with outcome of immunotherapy. Methods. Blood samples were taken antemortem from intact BLRB males and thirteen serum biochemical parameters were individually measured. Two weeks later syngeneic tumor cells were inoculated to males. Tumor-bearing mice were treated with IL-2 twice on day 13 and 22 after tumor cell inoculation; control group was treated with physiological solution. Results. We showed that only 63% of treated mice comprised beneficial subgroup. Negative effect of IL-2 was related to distinct initial serum biochemical parameter values that were indicative for liver pathology. Conclusion. The new 3S-paradigm was useful to show both positive and negative effects of IL-2 treatment. Revealed serum biochemical parameters could be considered as surrogate markers of immunotherapy efficacy in this model.