Skip to main content
Top
Published in: BMC Medical Informatics and Decision Making 1/2012

Open Access 01-12-2012 | Research article

Optimal vaccination schedule search using genetic algorithm over MPI technology

Authors: Cristiano Calonaci, Ferdinando Chiacchio, Francesco Pappalardo

Published in: BMC Medical Informatics and Decision Making | Issue 1/2012

Login to get access

Abstract

Background

Immunological strategies that achieve the prevention of tumor growth are based on the presumption that the immune system, if triggered before tumor onset, could be able to defend from specific cancers. In supporting this assertion, in the last decade active immunization approaches prevented some virus-related cancers in humans. An immunopreventive cell vaccine for the non-virus-related human breast cancer has been recently developed. This vaccine, called Triplex, targets the HER-2-neu oncogene in HER-2/neu transgenic mice and has shown to almost completely prevent HER-2/neu-driven mammary carcinogenesis when administered with an intensive and life-long schedule.

Methods

To better understand the preventive efficacy of the Triplex vaccine in reduced schedules we employed a computational approach. The computer model developed allowed us to test in silico specific vaccination schedules in the quest for optimality. Specifically here we present a parallel genetic algorithm able to suggest optimal vaccination schedule.

Results & Conclusions

The enormous complexity of combinatorial space to be explored makes this approach the only possible one. The suggested schedule was then tested in vivo, giving good results. Finally, biologically relevant outcomes of optimization are presented.
Appendix
Available only for authorised users
Literature
1.
go back to reference Castiglione F, Motta S, Pappalardo F, Pennisi M: A modeling framework for immune-related diseases. Math Modell Nat Phenom. 2012, 7 (3): 40-48. 10.1051/mmnp/20127304.CrossRef Castiglione F, Motta S, Pappalardo F, Pennisi M: A modeling framework for immune-related diseases. Math Modell Nat Phenom. 2012, 7 (3): 40-48. 10.1051/mmnp/20127304.CrossRef
2.
go back to reference Agur Z: Biomathematics in the development of personalized medicine in oncology. Future oncology. 2006, 2 (1): 39-42. 10.2217/14796694.2.1.39.CrossRefPubMed Agur Z: Biomathematics in the development of personalized medicine in oncology. Future oncology. 2006, 2 (1): 39-42. 10.2217/14796694.2.1.39.CrossRefPubMed
3.
go back to reference Pappalardo F, Palladini A, Pennisi M, Castiglione F, Motta S: Mathematical and computational models in tumor immunology. Math Modell Nat Phenom. 2012, 7 (3): 186-203. 10.1051/mmnp/20127312.CrossRef Pappalardo F, Palladini A, Pennisi M, Castiglione F, Motta S: Mathematical and computational models in tumor immunology. Math Modell Nat Phenom. 2012, 7 (3): 186-203. 10.1051/mmnp/20127312.CrossRef
4.
go back to reference Alemani D, Pappalardo F, Pennisi M, Motta S, Brusic V: Combining cellular automata and lattice boltzmann method to model multiscale avascular tumor growth coupled with nutrient diffusion and immune competition. J Immunological Methods. 2012, 376: 55-68. 10.1016/j.jim.2011.11.009.CrossRefPubMed Alemani D, Pappalardo F, Pennisi M, Motta S, Brusic V: Combining cellular automata and lattice boltzmann method to model multiscale avascular tumor growth coupled with nutrient diffusion and immune competition. J Immunological Methods. 2012, 376: 55-68. 10.1016/j.jim.2011.11.009.CrossRefPubMed
5.
go back to reference Pappalardo F, Lollini PL, Castiglione F, Motta S: Modeling and simulation of cancer immunoprevention vaccine. Bioinformatics. 2005, 21 (12): 2891-2897. 10.1093/bioinformatics/bti426.CrossRefPubMed Pappalardo F, Lollini PL, Castiglione F, Motta S: Modeling and simulation of cancer immunoprevention vaccine. Bioinformatics. 2005, 21 (12): 2891-2897. 10.1093/bioinformatics/bti426.CrossRefPubMed
7.
go back to reference Pappalardo F, Halling-Brown MD, Rapin N, Zhang P, Alemani D, Emerson A, Paci P, Duroux P, Pennisi M, Palladini A, Miotto O, Churchill D, Rossi E, Shepherd AJ, Moss DS, Castiglione F, Bernaschi M, Lefranc MP, Bruna S, Motta S, Lollini PL, Basford KE, Brusic V: Immunogrid, an integrative environment for large-scale simulation of the immune system for vaccine discovery, design and optimization. Briefings in Bioinf. 2009, 10 (3): 330-340.CrossRef Pappalardo F, Halling-Brown MD, Rapin N, Zhang P, Alemani D, Emerson A, Paci P, Duroux P, Pennisi M, Palladini A, Miotto O, Churchill D, Rossi E, Shepherd AJ, Moss DS, Castiglione F, Bernaschi M, Lefranc MP, Bruna S, Motta S, Lollini PL, Basford KE, Brusic V: Immunogrid, an integrative environment for large-scale simulation of the immune system for vaccine discovery, design and optimization. Briefings in Bioinf. 2009, 10 (3): 330-340.CrossRef
8.
go back to reference Pennisi M, Catanuto R, Pappalardo F, Motta S: Optimal vaccination schedules using simulated annealing. Bioinformatics. 2008, 24 (15): 1740-1742. 10.1093/bioinformatics/btn260.CrossRefPubMed Pennisi M, Catanuto R, Pappalardo F, Motta S: Optimal vaccination schedules using simulated annealing. Bioinformatics. 2008, 24 (15): 1740-1742. 10.1093/bioinformatics/btn260.CrossRefPubMed
9.
go back to reference Halling-Brown M, Pappalardo F, Rapin N, Zhang P, Alemani D, Emerson A, Castiglione F, Duroux P, Pennisi M, Miotto O, Churchill D, Rossi E, Moss DS, Sansom CE, Bernaschi M, Lefranc MP, Brunak S, Lund O, Motta S, Lollini PL, Murgo A, Palladini A, Basford KE, Brusic V, Shepherd AJ: Immunogrid: towards agent-based simulations of the human immune system at a natural scale. Philos Trans Royal Soc A: Math, Phys Eng Sci. 2010, 368 (1920): 2799-2815. 10.1098/rsta.2010.0067.CrossRef Halling-Brown M, Pappalardo F, Rapin N, Zhang P, Alemani D, Emerson A, Castiglione F, Duroux P, Pennisi M, Miotto O, Churchill D, Rossi E, Moss DS, Sansom CE, Bernaschi M, Lefranc MP, Brunak S, Lund O, Motta S, Lollini PL, Murgo A, Palladini A, Basford KE, Brusic V, Shepherd AJ: Immunogrid: towards agent-based simulations of the human immune system at a natural scale. Philos Trans Royal Soc A: Math, Phys Eng Sci. 2010, 368 (1920): 2799-2815. 10.1098/rsta.2010.0067.CrossRef
11.
go back to reference Palladini A, Nicoletti G, Pappalardo F, Murgo A, Grosso V, Stivani V, Ianzano ML, Antognoli A, Croci S, Landuzzi L, De Giovanni C, Nanni P, Motta S, Lollini PL: In silico modeling and in vivo efficacy of cancer-preventive vaccinations. Cancer Res. 2010, 70 (20): 7755-7763. 10.1158/0008-5472.CAN-10-0701.CrossRefPubMed Palladini A, Nicoletti G, Pappalardo F, Murgo A, Grosso V, Stivani V, Ianzano ML, Antognoli A, Croci S, Landuzzi L, De Giovanni C, Nanni P, Motta S, Lollini PL: In silico modeling and in vivo efficacy of cancer-preventive vaccinations. Cancer Res. 2010, 70 (20): 7755-7763. 10.1158/0008-5472.CAN-10-0701.CrossRefPubMed
12.
go back to reference Abbas AK, Litchman AH, Pillai S: Cellular and molecular immunology. 2011, Philadelphia, PA, USA: Elsevier Abbas AK, Litchman AH, Pillai S: Cellular and molecular immunology. 2011, Philadelphia, PA, USA: Elsevier
13.
go back to reference Cavallo F, De Giovanni C, Nanni P, Forni G, Lollini PL: 2011: the immune hallmarks of cancer. Cancer Immunol Immunother. 2011, 60: 319-326. 10.1007/s00262-010-0968-0.CrossRefPubMedPubMedCentral Cavallo F, De Giovanni C, Nanni P, Forni G, Lollini PL: 2011: the immune hallmarks of cancer. Cancer Immunol Immunother. 2011, 60: 319-326. 10.1007/s00262-010-0968-0.CrossRefPubMedPubMedCentral
14.
go back to reference Dunn GP, Old LJ, Schreiber RD: The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004, 21: 137-148. 10.1016/j.immuni.2004.07.017.CrossRefPubMed Dunn GP, Old LJ, Schreiber RD: The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004, 21: 137-148. 10.1016/j.immuni.2004.07.017.CrossRefPubMed
15.
go back to reference Finn OJ: Cancer immunology. N Eng J Med. 2008, 358: 2704-2715. 10.1056/NEJMra072739.CrossRef Finn OJ: Cancer immunology. N Eng J Med. 2008, 358: 2704-2715. 10.1056/NEJMra072739.CrossRef
16.
go back to reference Lollini PL, Cavallo F, Nanni P, Forni G: Vaccines for tumour prevention. Nat Rev Cancer. 2006, 6 (3): 204-216. 10.1038/nrc1815.CrossRefPubMed Lollini PL, Cavallo F, Nanni P, Forni G: Vaccines for tumour prevention. Nat Rev Cancer. 2006, 6 (3): 204-216. 10.1038/nrc1815.CrossRefPubMed
17.
go back to reference Nanni P, Nicoletti G, De Giovanni C, Landuzzi L, Di Carlo E, Cavallo F, Pupa SM, Rossi I, Colombo MP, Ricci C, Astolfi A, Musiani P, Forni G, Lollini PL: Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in her-2/neu transgenic mice. J Exp Med. 2001, 194 (9): 1195-1205. 10.1084/jem.194.9.1195.CrossRefPubMedPubMedCentral Nanni P, Nicoletti G, De Giovanni C, Landuzzi L, Di Carlo E, Cavallo F, Pupa SM, Rossi I, Colombo MP, Ricci C, Astolfi A, Musiani P, Forni G, Lollini PL: Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in her-2/neu transgenic mice. J Exp Med. 2001, 194 (9): 1195-1205. 10.1084/jem.194.9.1195.CrossRefPubMedPubMedCentral
18.
go back to reference Novellino L, Castelli C, Parmiani G: A listing of human tumor antigens recognized by t cells. Cancer Immunol Immunother. 2005, 54: 187-207. 10.1007/s00262-004-0560-6.CrossRefPubMed Novellino L, Castelli C, Parmiani G: A listing of human tumor antigens recognized by t cells. Cancer Immunol Immunother. 2005, 54: 187-207. 10.1007/s00262-004-0560-6.CrossRefPubMed
19.
go back to reference Lollini PL, Nicoletti G, Landuzzi L, Cavallo F, Forni G, De Giovanni C, Nanni P: Vaccines and other immunological approaches for cancer immunoprevention. Curr Drug Targets. 2010, 12: 1957-1973.CrossRef Lollini PL, Nicoletti G, Landuzzi L, Cavallo F, Forni G, De Giovanni C, Nanni P: Vaccines and other immunological approaches for cancer immunoprevention. Curr Drug Targets. 2010, 12: 1957-1973.CrossRef
20.
go back to reference Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WK, Stuart SG, Udove J, Ullrich A: Studies of the her-2/neu protooncogene in human breast and ovarian cancer. Science. 1989, 244: 707-712. 10.1126/science.2470152.CrossRefPubMed Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WK, Stuart SG, Udove J, Ullrich A: Studies of the her-2/neu protooncogene in human breast and ovarian cancer. Science. 1989, 244: 707-712. 10.1126/science.2470152.CrossRefPubMed
21.
go back to reference Ursini-Siegel J, Schade B, Cardiff RD, Muller WJ: Insights from transgenic mouse models of erbb2-induced breast cancer. Nat Rev Cancer. 2007, 7: 389-397. 10.1038/nrc2127.CrossRefPubMed Ursini-Siegel J, Schade B, Cardiff RD, Muller WJ: Insights from transgenic mouse models of erbb2-induced breast cancer. Nat Rev Cancer. 2007, 7: 389-397. 10.1038/nrc2127.CrossRefPubMed
22.
go back to reference De Giovanni C, Nicoletti G, Landuzzi L, Astolfi A, Croci S, Comes A, Ferrini S, Meazza R, Iezzi M, Di Carlo E, Musiani P, Cavallo F, Nanni P, Lollini PL: Immunoprevention of her-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine. Cancer Res. 2004, 64 (11): 4001-4009. 10.1158/0008-5472.CAN-03-2984.CrossRefPubMed De Giovanni C, Nicoletti G, Landuzzi L, Astolfi A, Croci S, Comes A, Ferrini S, Meazza R, Iezzi M, Di Carlo E, Musiani P, Cavallo F, Nanni P, Lollini PL: Immunoprevention of her-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine. Cancer Res. 2004, 64 (11): 4001-4009. 10.1158/0008-5472.CAN-03-2984.CrossRefPubMed
23.
go back to reference Nanni P, Nicoletti G, Palladini A, Croci S, Murgo A, Antognoli A, Landuzzi L, Fabbi M, Ferrini S, Musiani P, Iezzi M, De Giovanni C, Lollini PL: Antimetastatic activity of a preventive cancer vaccine. Cancer Res. 2007, 67: 11037-11044. 10.1158/0008-5472.CAN-07-2499.CrossRefPubMed Nanni P, Nicoletti G, Palladini A, Croci S, Murgo A, Antognoli A, Landuzzi L, Fabbi M, Ferrini S, Musiani P, Iezzi M, De Giovanni C, Lollini PL: Antimetastatic activity of a preventive cancer vaccine. Cancer Res. 2007, 67: 11037-11044. 10.1158/0008-5472.CAN-07-2499.CrossRefPubMed
24.
go back to reference Bianca C, Pennisi M: The triplex vaccine effects in mammary carcinoma: a nonlinear model in tune with simtriplex. Nonlinear Analysis: Real World Applications. 2012, 13: 1913-1940. 10.1016/j.nonrwa.2011.12.019.CrossRef Bianca C, Pennisi M: The triplex vaccine effects in mammary carcinoma: a nonlinear model in tune with simtriplex. Nonlinear Analysis: Real World Applications. 2012, 13: 1913-1940. 10.1016/j.nonrwa.2011.12.019.CrossRef
25.
go back to reference Bianca C, Pennisi M, Motta S, Ragusa MA: Immune system network and cancer vaccine. International Conference on Numerical Analysis and Applied Mathematics: Numerical Analysis and Applied Mathematics, ICNAAM 2011, volume 1389, AIP Conference Proceedings. 2011, 945-948. Bianca C, Pennisi M, Motta S, Ragusa MA: Immune system network and cancer vaccine. International Conference on Numerical Analysis and Applied Mathematics: Numerical Analysis and Applied Mathematics, ICNAAM 2011, volume 1389, AIP Conference Proceedings. 2011, 945-948.
26.
go back to reference Lollini PL, Motta S, Pappalardo F: Modeling tumor immunology. Math Models & Methods Appl Sci. 2006, 16 (7S): 1091-1124.CrossRef Lollini PL, Motta S, Pappalardo F: Modeling tumor immunology. Math Models & Methods Appl Sci. 2006, 16 (7S): 1091-1124.CrossRef
27.
go back to reference Mitchell M: An Introduction to Genetic Algorithms. 1996, Boston, USA: The MIT Press Mitchell M: An Introduction to Genetic Algorithms. 1996, Boston, USA: The MIT Press
28.
go back to reference Goldberg DE: A comparative analysis of selection schemes used in genetic algorithms, Foundations of Genetic Algorithms. 1991, San Mateo, California, USA: Morgan Kaufmann Goldberg DE: A comparative analysis of selection schemes used in genetic algorithms, Foundations of Genetic Algorithms. 1991, San Mateo, California, USA: Morgan Kaufmann
29.
go back to reference Corne D, Dorigo M, Glove F: New ideas in optimization. 1999, McGraw-Hill: Advanced Topics in Computer Science Corne D, Dorigo M, Glove F: New ideas in optimization. 1999, McGraw-Hill: Advanced Topics in Computer Science
30.
go back to reference Pappalardo F, Pennisi M, Castiglione F, Motta S: Vaccine protocols optimization: In silico experiences. Biotechnol Adv. 2010, 28 (1): 82-93. 10.1016/j.biotechadv.2009.10.001.CrossRefPubMed Pappalardo F, Pennisi M, Castiglione F, Motta S: Vaccine protocols optimization: In silico experiences. Biotechnol Adv. 2010, 28 (1): 82-93. 10.1016/j.biotechadv.2009.10.001.CrossRefPubMed
Metadata
Title
Optimal vaccination schedule search using genetic algorithm over MPI technology
Authors
Cristiano Calonaci
Ferdinando Chiacchio
Francesco Pappalardo
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Medical Informatics and Decision Making / Issue 1/2012
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/1472-6947-12-129

Other articles of this Issue 1/2012

BMC Medical Informatics and Decision Making 1/2012 Go to the issue