Discovery of cancer vaccination protocols with a genetic algorithm driving an agent based simulator.
BACKGROUND
Immunological prevention of cancer has been obtained in HER-2/neu transgenic mice using a vaccine that combines 3 different immune stimuli (Triplex vaccine) that is repeatedly administered for the entire lifespan of the host (Chronic protocol). Biological experiments leave open the question of whether the Chronic protocol is indeed the minimal vaccination schedule affording 100% protection, or whether shorter protocols could be applied that would result in the same efficacy. A biological solution would require an enormous number of experiments, each lasting at least one year. Therefore we approached this problem by developing a simulator (SimTriplex) which describes the immune response activated by Triplex vaccine. This simulator, tested against in vivo experiments on HER-2/neu mice, reproduces all the vaccination protocols used in the in vivo experiments. The simulator should describe any vaccination protocol within the tested range. A possible solution to the former open question using a minimal search strategy based on a genetic algorithm is presented. This is the first step toward a more general approach of biological or clinical constraints for the search of an effective vaccination schedule.


RESULTS
The results suggest that the Chronic protocol included a good number of redundant vaccine administrations, and that maximal protection could still be obtained with a number of vaccinations approximately 40% less than with the Chronic protocol.


CONCLUSIONS
This approach may have important connotations with regard to translation of cancer immunopreventive approaches to human situations, in which it is desirable to minimize the number of vaccinations. We are currently setting up experiments in mice to test whether the actual effectiveness of the vaccination protocol agrees with the genetic algorithm.
Lollini
Pier-Luigi
PL
Sezione di Cancerologia, Dipartimento di Patologia Sperimentale, University of Bologna, Italy. pierluigi.lollini@unibo.it
Motta
Santo
S
Pappalardo
Francesco
F
D000465:Algorithms; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003198:Computer Simulation; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D005103:Expert Systems; D007115:Immunization Schedule; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008957:Models, Genetic; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D019496:Cancer Vaccines