Methods and Results

We have developed a mathematical model that encompasses basic interactions of the vaccine, immune cells and cancer cells (Figure 1). Data obtained from published preclinical and laboratory experiments were used for estimation of most model parameters. The model was successfully validated using clinical data from a phase 2 trial testing an allogeneic PCa whole–cell vaccine (Michael, et al., 2005). We evaluated selected patient–specific parameters, using “training data” consisting of prostate–specific antigen (PSA) levels recorded prior to and during the early stages of vaccination treatment in each of the phase-2 trial patients. Subsequently, the model was simulated to yield patient–specific PSA dynamics in the later stages of therapy, and compared these predictions with the clinically measured PSA values (“validation data”). By using only nine to 15 initial PSA measurements (six to ten of which were initial in–treatment values) for training, we arrived at a model that accurately and robustly described the entire course of PSA dynamics in the 12 of 15 vaccination–responsive patients (R2=0.972). Interestingly, we discovered that the number of training data required for validation differed among patients, emphasizing the importance of patient–specific analysis.