Current Trends in Cancer Vaccines - a Bioinformatics Perspective

  • Sankar, Shanju (Division of Biochemistry, Malabar Cancer Center) ;
  • Nayanar, Sangeetha K. (Department of Oncopathology, Malabar Cancer Center) ;
  • Balasubramanian, Satheesan (Department of Surgical Oncology, Malabar Cancer Center)
  • Published : 2013.07.30


Cancer vaccine development is in the process of becoming reality in future, due to successful phase II/III clinical trials. However, there are still problems due to the specificity of tumor antigens and weakness of tumor associated antigens in eliciting an effective immune response. Computational models to assess the vaccine efficacy have helped to improve and understand what is necessary for personalized treatment. Further research is needed to elucidate the mechanisms of activation of antigen specific cytotoxic T lymphocytes, decreased TREG number functionality and antigen cascade, so that overall improvement in vaccine efficacy and disease free survival can be attained. T cell epitomic based in sillico approaches might be very effective for the design and development of novel cancer vaccines.


  1. Alemani D, Pappalardo F, Pennissi M, Motta S, Brusic V (2012). Combining cellular automata and lattice boltzman method to model multiscale avascular tumour growth coupled with nutrient diffusion and immune competition. J Immunol Methods, 376, 55-68.
  2. Ai WZ, Tibshirani R, Taidi B, Czerwinski D, Levy R (2009) Anti-Idiotype antibody response after vaccination correlates with better overall survival in follicular lymphoma. Blood, 113, 5743-6.
  3. Akahata W, Yang ZY, Andersen H, et al (2010). A virus like particle vaccine for epidemic chikungunya virus protects non-human primates against infection. Nat Med, 16, 334-8.
  4. Atanasova M, Dimitrov I, Flower DR, Doytchinova I (2011). MHC class I binding prediction by molecular docking. Molecular Informatics, 30, 368-75.
  5. Begley J, Ribas A (2008). Targeted therapies to improve tumor immunotherapy. Clin Cancer Res, 14, 4385-91
  6. Bhattacharya M-Chatterjee, Chatterjee SK, Foon KA (2002). Anti-idiotype antibody vaccine therapy for cancer. Expert Opin Biol Ther, 2, 869-81
  7. Bendle GM, Holler A, Downs A-M, Xue S-A, Stauss SJ (2005). Broadly expressed tumor associated proteins as targets for cytotoxic T lymphocyte based cancer immunotherapy. Expert Opin Biol Ther, 5, 1183-92.
  8. Bolhassini A, Rafati S (2008). Heat shock proteins as powerful weapons in vaccine development. Expert Rev Vacc, 7, 1185-99.
  9. Butts CM, Maksyumuk A, Goss G (2007). A multicenter Phase II randomized controlled study of BLP25 liposome vaccine (stimuvax) against non small cell lung cancer updated survival analysis. J Thorac Oncol, 2, 332-3.
  10. Best SR, Peng S, Juang C-M, et al (2009). Administration of HPV DNA vaccine via electroporation elicts the strongest CD 8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery. Vaccine, 27, 5450-9.
  11. Binder RJ, Srivastava PK (2005). Peptides chaeperoned by heat shock proteins are a necessary and sufficient source of antigen in the cross priming of CD 8+ T cells. Nat Immunol. 6, 593-9.
  12. Brusic V, Petrovsky N (2005). Immunoinformatics and its relevance to human clinical diseases. Expert Rev Clin Immunol, 1, 145-57.
  13. Chang Y, Brewer NT, Rinas AC, Schmitt K, Smith JS (2009). Evaluating the impact of Human papillomavirus vaccines. Vaccine, 27, 4355-62.
  14. Cerundolo V, Hermann IF, Salio M (2004). Dendritic cell- a journey from laboratory to clinic. Nat Immunol, 5, 7-10.
  15. Conry RM, Curiel DT, Strong TV (2002). Safety and Immunogenicity of DNA vaccine encoding carcinoembryonic antigen and Hepatitis B surface antigen in colorectal carcinoma patients. Clin Cancer Res, 8, 2782-7.
  16. Caruso DA, Orme LM, Neale AM (2004). Results of Phase 1 study utilizing monocyte derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer. Neuro-Oncol, 6, 236-46.
  17. Caruso DA, Orme LM, Amor GM (2005). Results of Phase 1 study utilizing monocyte derived dendritic cells pulsed with tumor RNA in children and young adults with stage 4 of the neuroblatoma. Cancer, 103, 1280-91.
  18. Danull J, Su Z, Rizzieri D (2005). Enhancement of vaccine mediated antitumor immunity in patients after depletion of regulatory T cells. J Cancer Invest. 115, 3623-33.
  19. Dunn GP, Old LJ, Schreiber RD (2004). The three E's of Cancer Immunoediting. Annu Rev Immunol, 22, 329-60.
  20. Dougan M, Dranoff G (2009). Immune therapy for cancer. Annu Rev Immunol, 27, 83-117.
  21. Doehn C, Richter A, Theodor R, Lehmacher W, Jocham D (2006). Prolongation of progression free and overall survival following an adjuvant vaccination with reniale in patients with metastatic renal cell carcinoma: secondary analysis of Multicenter Phase 3 trial in Proceedings of German Cancer Congress Programmed and Abstracts
  22. Geary SM, Lemke CD, Lubaroff DM, Salem AK (2013) Nat Rev Urol Mar, 10, 149-60.
  23. Geary SM, Salem AK (2013). Prostrate cancer vaccine: update on clinical development. Oncoimmunology, 2, 24525
  24. Guinn BA, Kasahara N, Farzaneh F, et al (2007). Recent advances and current challenges in tumor immunology and immunotherapy. Mol ther, 15, 1065-71.
  25. Goldmann B, Defrancesco L (2009). The Cancer Vaccine Roller Coaster. Nat Biotechnol, 27, 129-39.
  26. Gulley J, Chen AP, Dahut W, et al (2002). Phase 1 study of vaccine using recombinant vaccinia virus expressing PSA in patients with metastatic androgen independent prostrate specific cancer. Prostrate, 53, 109-17.
  27. Hellstorm KE, Hellstorm I (2003). Novel approach to therapeutic cancer vaccines. Expert Rev Vacc, 2, 517-32.
  28. He Y, Rappuoli R, De Groot AS, Chen RT (2010). Emerging vaccine informatics. J Biomed Biotechnol, 218590, 26.
  29. Harper DM, Franco EL, Wheeler C, et al (2004). Efficacy of a bivalent virus L1 virus like particle vaccine in prevention of infection with human pappilloma virus types 16 and 18 in young women: a randomized controlled trial. Lancet, 364, 1757-65.
  30. Higano CS, Schellhammer PF, Small EJ (2009). Integrated data from 2 randomized double blind, Placebo controlled Phase 3 trails of active cellular Immunotherapy with Sipuleucel-T in patients with advanced prostate cancer. Cancer, 115, 3670-9.
  31. Hamilton SE, Wolkers MC, Schoenberger SP, Jameson SC (2006). The generation of Protective memory like CD 8+ T cells during homeostatic proliferation requires CD 4+ T cells. Nat Immunol, 7, 475-81.
  32. Hodi FS, Butler M, Oble DA, et al (2008). Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte Associated Antigen-4 in previously vaccinated Cancer Patients. Proc Natl Acad Sci USA, 105, 3005-10.
  33. Huyang YL, Hung JT, Cheung SK, et al (2013). Carbohydrate based vaccine with glycolipid as adjuvant against the breast cancer. Proc Natl Acad Sci USA, 110, 2517-22.
  34. Jenner E (1798). An Inquiry into the causes and effects of variola vaccine, a disease discovered in some of western countries of England, Particularly gloucesteshire and known by the name of cowpox. London: Sampson low.
  35. Joshi B, Wang X, Banerjee S, et al (2009). On immunotherapies and cancer vaccination protocol. J Theor Biol, 259, 820-7.
  36. Jemel A, Siegel R, Ward E, et al (2009). Cancer statistics 2009. CA Cancer J Clin, 59, 225-49.
  37. Jakob CO, Leitner M, Zamir A, Salomon D, Arnon R (1985). Priming immunization against cholera toxin and ecoli heat labile toxin by cholera toxin short peptide galactosidase hybrid synthesized in ecoli. EMBO J, 4, 3339-43.
  38. Janeaway CA, Travers P, Walport M, Shlomchick M (2001). Immunobiology: the immune system in health and disease. New York. Churchil and Livingstone.
  39. Joyce S, Nathenson SG (1994). Methods to Study peptides associated with MHC class I molecules. Curr Opin Immunol. 6, 24-31.
  40. Kumar N, Henriks BS, Janes KA, de Graff D, Laufenburger DA (2006). Applying computational modeling to drug development and Discovery. Drug Discovery Today, 11, 806-11.
  41. Kogan Y, Halevi-Tobias K, Elishmereni M, Vuk-Pavlovic, Agur Z (2012). Reconsidering the paradigm of cancer immunotherapy by computer aided real-time personalization. Cancer Res, 72, 2218-27.
  42. Kantor J, Abrams S, Irvine K, et al (1993). Specific Immunotherapy using recombinant vaccinia virus expressing human carcinoembryonic antigen. Ann New York Acad Sci, 690, 370-3
  43. Kass E, Schlom J, Thomson F, et al (1999). Induction of host Immunity to human carcinogenic antigen, a self antigen in CEA transgenic mice by immunizing with recombinant vaccinia-CEA virus. Cancer Res, 59, 676-83.
  44. Kreig PA, Melton DA (1984). Functional messanger RNA s are produced by SP 6, invitro transcription of cloned cDNA s. Nucleic Acid Res. 12, 7057-70.
  45. Lollini PL, Cavallo F, Nanni P, Forni G (2006). Vaccines for tumour prevention Nature Cancer Rev, 6, 204-16.
  46. Lurescia S, Fioretti D, Fazio VM, Rinaldi M (2012). Epitope driven DNA vaccine design employing immunoinformatics against B-cell lymphoma: a biotech challenge. Biotechnol Adv, 30, 372-83.
  47. Letvin NL, Walker BD (2001). HIV versus Immune system: another apparent victory for the virus. J Clin Investi, 107, 273-5.
  48. Mishra S, Sinha S (2009). Immunoinformatics and modeling perspective of T cell epitope based cancer immunotherapy: a holistic picture. J Biomol Struct Dyn, 27, 293-306.
  49. Mortimer PP (2003). Can Post exposure against small pox vaccination succeed. Clin Infec Dieseases, 36, 622-9.
  50. Michluart P, Abdullah KA, Lima FD (2008). Phase 1 trial of DNA HSP 65 immunotherapy for advanced squamous cell carcinoma of head and neck. Cancer Gene Ther, 15, 676-84.
  51. Morse MA, Nair SK, Mosca PJ (2003). Immunotherapy with dendridic cells infected with carcinoembryonic antigen mRNA. Cancer Invest, 21, 341-9.
  52. Manam S, Ledwith BJ, Barnum AB, et al (2000). Plasmid DNA vaccine: Tissue distribution and Effects of DNA sequence, adjuvants and delivery methods of integration into host DNA. Intervirology, 43, 273-81.
  53. Meloen RH, Langeveld JP, Schaaper WM, Slootstra JW (2001). Synthetic peptide vaccines: unexpected fulfillment of discarded hope? Biologicals, 29, 233-6.
  54. Madden DR (1995). The three dimensional structure of Peptide-MHC complexes. Annu Rev Immunol, 13, 587-622.
  55. Mamitsuka (1998). Predicting peptides that bind to MHC molecules using supervised learning of hidden markov models. Proteins, 33, 460-74.<460::AID-PROT2>3.0.CO;2-M
  56. Nanni L (2006). Machine learning algorithms for T cell epitope prediction. Neurocomputing, 69, 866-8.
  57. Naz RK, Dabir P (2007). Peptide vaccine against cancer, Infectious diseases and conception. Front Biosci, 12, 1833-44.
  58. Nestle FO, Farkas A, Conrad C (2005). Dendritic cell based therapeutic vaccination against cancer. Curr Opin Immunol, 17, 163-9.
  59. Ostrnad-Rosenberg S (2008). Immune surveillance- a balance between protumour and anti tumor immunity. Cur Opin Genet Dev, 18, 11-8.
  60. Pappalardo F, Chiacchio F, Motta S (2013). Cancer vaccine-state of the art of computational Modeling approaches. Biomed Res Int, 106407, 6
  61. Pappalardo F, Lollini PL, Castiglione F, Motta S (2005). Modelling and simulation of cancer immunoprevention vaccine. Bioinformatics, 21, 2891-7.
  62. Palladini A, Nicoletti G, Pappalardo F, et al (2010). In sillico modeling and in vivo efficacy of cancer preventive vaccinations. Cancer Res, 70, 7755-63.
  63. Pappalardo F, Pennisi M, Castiglione F, Motta S (2010). Vaccine protocols optimization: in silicon experiences. Biotechnol Adv, 28, 82-93.
  64. Pennisi M, Catanuto R, Pappalaroda F, Motta S (2008). Optimal vaccination schedules using simulated annealing. Bioinformatics, 24, 1740-52.
  65. Palena C, Abrams SI, Schlom J, hodge JW (2006). Cancer vaccines: preclinical studies and novel strategies. Adv Cancer Res, 95, 115-45.
  66. Palena C, Polev DV, Tsang KY, et al (2007). The human t box mesodermal transcription factor brachyury is a candidate target for T cell mediated cancer immunotherapy. Clin Cancer Res, 13, 2471-8.
  67. Pasquini S, Xiang Z, Wang Y (1997). Cytokines and CO stimulatory molecules as genetic adjuvant. Immunol Cell Biol. 75, 397-401.
  68. Pavlenko M, Roos A-K, Lundqvist K et al (2004). A phase 1 trial of DNA vaccination with plasmid expressing prostate specific antigen in patients with hormone refractory prostate cancer. Bri J Cancer, 91, 688-94
  69. Pascolo S (2004). Messenger-RNA based Vaccines. Expert Opin Biol Ther, 4, 1285-94.
  70. Payette PJ, Davis HL (2001). History of vaccines and positioning of current trends. Curr Drug Targets Infect Disord, 1, 241-7.
  71. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S (1999). SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics, 50, 213-9.
  72. Sezerman U, Vajda S, Cornette J, Delissi C (1993). Toward computational determination of Peptide receptor structure. Protein Sci, 2, 1827-43.
  73. Schietinger A, Philip M, Schreiber H (2008) Specificity in cancer immunotherapy. Semin Immunol, 20, 276-85.
  74. Silva JM, Videira M, Gaspar R, Preat V, Florino HF (2013). Immune system targeting by biodegradable nanoparticle for cancer vaccine. J Control Release, 168, 179-99.
  75. Danhier F, Ansorena E, Silva JM, et al (2012). PLGA based nanoparticles: an overview of biomedical applications. J Control Release, 161, 505-22.
  76. Su Z, Dannull J, Yang BK (2005). Telomerase mRNA transfected dendritic cells stimulate antigen specific CD 8+ and CD 4+ T cell responses in patients with metastatic prostate cancer. J Immunol, 174, 3798-807
  77. Szmuness W, Stevens CE, Oleszko WR, Goodman A, (1981). Passive-active immunization against Hepatitis B: Immunogenicity studies in adult Americans. Lancet, 1, 575-7.
  78. Terasawa H, Tsang KY, Gulley J, Arlen P, Schlom J (2002). Identification and characterization of human agonist cytotoxic T lymphocyte epitope of human prostate specific antigen. Clin Cancer Res, 8, 41-53.
  79. Tomar N, De RK (2010). Immunoinformatics: Integrated scenario. Immunol, 113, 153-68.
  80. U'Ren L, Kedl R, Dow S (2006). Vaccination with liposome DNA complexes elicts enhanced antitumor immunity. Cancer Gene Ther, 13, 1033-44.
  81. Van der bruggen P, Traversari C, Chomez P (1991). A gene encoding an antigen recognized by Cyotoxic T lymphocytes on a human melanoma. Science, 254, 1643-7.
  82. Vermorken JB, Claessen AM E, Van tinteren, et al (1999). Active specific immunotherapy for stage 2 and stage 3 human colon cancer: a randomized trial. Lancet, 353, 345-50.
  83. Wilson S, Levy D (2012). A mathematical model of enhancement of tumor vaccine efficacy by Immunotherapy. Bull Math Biol, 74, 1485-500.
  84. Yuan J, Ku GY, Gallardo HF, et al (2009). Safety and Immunogenicity of human and mouse gp 100 DNA vaccine in phase 1 trial of patients with melanoma. Cancer Immun, 9, 5.
  85. Zhou J, Sun XY, Stenzel DJ, Frazer IH (1991) Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion like particles. Vir, 185, 251-7.
  86. Zaremba S, Barzaga E, Zhu M et al (1997) Identification of enhancer agonist cytotoxic T lymphocyte peptide from carcinoembryonic antigen. Cancer Res, 57, 4570-7.
  87. Campoli M, Ferrone S (2008). HLA antigen changes in malignant cells: Epigenetic mechanism and biological significance. Oncogene, 27, 5869-85.

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