Skip to main content

In Silico-Guided Sequence Modification of Epitopes in Cancer Vaccine Development

  • Protocol
  • First Online:
Immunoinformatics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2131))

Abstract

Discovery of tumor antigenic epitopes is important for cancer vaccine development. Such epitopes can be designed and modified to become more antigenic and immunogenic in order to overcome immunosuppression towards the native tumor antigen. In silico-guided modification of epitope sequences allows predictive discrimination of those that may be potentially immunogenic. Therefore, only candidates predicted with high antigenicity will be selected, constructed, and tested in the lab. Here, we described the employment of in silico tools using a multiparametric approach to assess both potential T-cell epitopes (MHC class I/II binding) and B-cell epitopes (hydrophilicity, surface accessibility, antigenicity, and linear epitope). A scoring and ranking system based on these parameters was developed to shortlist potential mimotope candidates for further development as peptide cancer vaccines.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Pietersz GA, Pouniotis DS, Apostolopoulos V (2006) Design of peptide-based vaccines for cancer. Curr Med Chem 13(14):1591–1607. https://doi.org/10.2174/092986706777441922

    Article  CAS  PubMed  Google Scholar 

  2. Li W, Joshi MD, Singhania S, Ramsey KH, Murthy AK (2014) Peptide vaccine: progress and challenges. Vaccines (Basel) 2(3):515–536. https://doi.org/10.3390/vaccines2030515

    Article  CAS  Google Scholar 

  3. Sharav T, Wiesmüller KH, Walden P (2007) Mimotope vaccines for cancer immunotherapy. Vaccine 25(16):3032–3037. https://doi.org/10.1016/j.vaccine.2007.01.033

    Article  CAS  PubMed  Google Scholar 

  4. Knittelfelder R, Riemer AB, Jensen-Jarolim E (2009) Mimotope vaccination—from allergy to cancer. Expert Opin Biol Ther 9(4):493–506. https://doi.org/10.1517/14712590902870386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Buhrman JD, Slansky JE (2013) Mimotope vaccine efficacy gets a "boost" from native tumour antigens. OncoImmunology 2(4):e23492. https://doi.org/10.4161/onci.23492

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lipford GB, Bauer S, Wagner H, Heeg K (1995) In vivo CTL induction with point-substituted ovalbumin peptides: immunogenicity correlates with peptide-induced MHC class I stability. Vaccine 13(3):313–320. https://doi.org/10.1016/0264-410x(95)93320-9

    Article  CAS  PubMed  Google Scholar 

  7. Pogue RR, Eron J, Frelinger JA, Matsui M (1995) Amino-terminal alteration of the HLA-A∗0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. Proc Natl Acad Sci U S A 92(18):8166–8170. https://doi.org/10.1073/pnas.92.18.8166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fikes J (2004) Chapter 2: the rational design of T cell epitopes with enhanced immunogenicity. In: Morse MA, Clay TM, Lyerly HK (eds) Handbook of cancer vaccines. Humana Press, New Jersey

    Google Scholar 

  9. Bei R, Scardino A (2010) TAA polyepitope DNA-based vaccines: a potential tool for cancer therapy. J Biomed Biotechnol:1–12. https://doi.org/10.1155/2010/102758

    Article  Google Scholar 

  10. Huarte E, Sarobe P, Lu J, Casares N, Lasarte JJ, Dotor J, Ruiz M, Prieto J, Celis E, Borrás-Cuesta F (2002) Enhancing immunogenicity of a CTL epitope from carcinoembryonic antigen by selective amino acid replacements. Clin Cancer Res 8(7):2336–2344

    CAS  PubMed  Google Scholar 

  11. Schreurs MWJ, Kueter EWM, Scholten KBJ, Lemonnier FA, Meijer CJLM, Hooiberg E (2005) A single amino acid substitution improves the in vivo immunogenicity of the HPV16 oncoprotein E7 (11-20) cytotoxic T lymphocyte epitope. Vaccine 23(31):4005–4010. https://doi.org/10.1016/j.vaccine.2005.03.014

    Article  CAS  PubMed  Google Scholar 

  12. Hofmann S, Mead A, Malinovskis A, Hardwick NR, Guinn BA (2015) Analogue peptides for the immunotherapy of human acute myeloid leukemia. Cancer Immunol Immunother 64(11):1357–1367. https://doi.org/10.1007/s00262-015-1762-9

    Article  CAS  PubMed  Google Scholar 

  13. Kumar SR, Prabakaran M, Ashok Raj KV, He F, Kwang J (2015) Amino acid substitutions improve the immunogenicity of H7N7HA protein and protect mice against lethal H7N7 viral challenge. PLoS One 10(6):e0128940. https://doi.org/10.1371/journal.pone.0128940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brown JH, Jardetzky TS, Gorga JC et al (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364(6432):33–39. https://doi.org/10.1038/364033a0

    Article  CAS  PubMed  Google Scholar 

  15. Parker JM, Guo D, Hodges RS (1986) New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X--ray--derived accessible sites. Biochemistry 25(19):5425–5432. https://doi.org/10.1021/bi00367a013

    Article  CAS  PubMed  Google Scholar 

  16. Levitt M (1978) Conformational preferences of amino acids in globular proteins. Biochemistry 17(20):4277–4285. https://doi.org/10.1021/bi00613a026

    Article  CAS  PubMed  Google Scholar 

  17. Kavitha K, Saritha R, Vinod Chandra S (2013) Computational methods in linear B--cell epitope prediction. Int J Comput Appl 63(12):28–32

    Google Scholar 

  18. Kolaskar AS, Tongaonkar PC (1990) A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett 276(1–2):172–174. https://doi.org/10.1016/0014-5793(90)80535-q

    Article  CAS  PubMed  Google Scholar 

  19. Emini EA, Hughes JV, Perlow DS, Boger J (1985) Induction of hepatitis a virus-neutralising antibody by a virus-specific synthetic peptide. J Virol 55(3):836–839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang ST, Ghosh D, Kirschner DE, Linderman JJ (2006) Peptide length-based prediction of peptide–MHC class II binding. Bioinformatics 22(22):2761–2767. https://doi.org/10.1093/bioinformatics/btl479

    Article  CAS  PubMed  Google Scholar 

  21. Srinivasan P, Kumar SP, Karthikeyan M et al (2011) Epitope-based immunoinformatics and molecular docking studies of nucleocapsid protein and ovarian tumor domain of crimean-Congo hemorrhagic fever virus. Front Genet 2:72. https://doi.org/10.3389/fgene.2011.00072

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ng AWR, Tan PJ, Hoo WPY et al (2018) In silico-guided sequence modifications of K-ras epitopes improve immunological outcome against G12V and G13D mutant KRAS antigens. PeerJ 6:e5056. https://doi.org/10.7717/peerj.5056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lionel L. A. In .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Hoo, W.P.Y., Siak, P.Y., In, L.L.A. (2020). In Silico-Guided Sequence Modification of Epitopes in Cancer Vaccine Development. In: Tomar, N. (eds) Immunoinformatics. Methods in Molecular Biology, vol 2131. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0389-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0389-5_10

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0388-8

  • Online ISBN: 978-1-0716-0389-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics