Abstract
In the last few years, the importance of neoepitopes for the development of personalized antitumor vaccines has increased remarkably. This kind of epitopes are considered to generate a strong immune reaction, while their non-mutated version, which sometimes differs only in a single amino-acid, does not generate a response at all. In order to study if, regardless the immune tolerance, neoepitopes are quantitatively more immunogenic than the original strings, we have obtained samples of mutated and non-mutated epitopes of six patients with cutaneous melanoma in different stages, and then we have compared them. More precisely, we have used several bioinformatic tools to study certain properties of the epitopes such as the HLA binding affinity of classes I and II, and found that some of them are in fact increased in their mutated versions, which supports the hypothesis, and also reinforces the use of neoepitopes for cancer vaccine design.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Vormehr, M., Diken, M., TĂŒreci, Ă., Sahin, U., Kreiter, S.: Personalized neo-epitope vaccines for cancer treatment. In: Theobald, M. (ed.) Current Immunotherapeutic Strategies in Cancer. RRCR, vol. 214, pp. 153â167. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-23765-3_5
Vermaelen, K.: Vaccine strategies to improve anti-cancer cellular immune responses. Front. Immunol. 10, 8 (2019). https://doi.org/10.3389/fimmu.2019.00008
Sahin, U., et al.: Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 7662 (2017)
Kakimi, K., Karasaki, T., Matsushita, H., Sugie, T.: Advances in personalized cancer immunotherapy. Breast Cancer 24, 16â24 (2017)
Stratton, M.R.: Exploring the genomes of cancer cells: progress and promise. Science 331, 1553â1558 (2011)
Kreiter, S., Castle, J.C., TĂŒreci, Ă., Sahin, U.: Targeting the tumor mutanome for personalized vaccination therapy. Oncoimmunology 1, 768â769 (2012)
Leclerc, M., et al.: Recent advances in lung cancer immunotherapy: input of T-cell epitopes associated with impaired peptide processing. Front. Immunol. 10, 1505 (2019)
Vormehr, M., TĂŒreci, Ă., Sahin, U.: Harnessing tumor mutations for truly individualized cancer vaccines. Annu. Rev. Med. 70, 395â407 (2019)
Tanyi, J.L., et al.: Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci. Transl. Med. 10, eaao5931 (2018)
Hu, Z., Ott, P.A., Wu, C.J.: Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat. Rev. Immunol. 18, 168 (2018)
Fritsch, E.F., Rajasagi, M., Ott, P.A., Brusic, V., Hacohen, N., Wu, C.J.: HLA-binding properties of tumor neoepitopes in humans. Cancer Immunol. Res. 2, 522â529 (2014)
Lundegaard, C., Lund, O., Nielsen, M.: Prediction of epitopes using neural network-based methods. J. Immunol. Methods 374, 26â34 (2011)
Zhang, Q., et al.: Immune epitope database analysis resource (IEDB-AR). Nucl. Acids Res. 36, 513â518 (2008)
Soria-Guerra, R.E., Nieto-Gomez, R., Govea-Alonso, D.O., Rosales-Mendoza, S.: An overview of bioinformatics tools for epitope prediction: implications on vaccine development. J. Biomed. Inform. 53, 405â414 (2015)
MartĂnez, L., MilaniÄ, M., Malaina, I., Ălvarez, C., PĂ©rez, M.B., Ildefonso, M.: Weighted lambda superstrings applied to vaccine design. PLoS ONE 14, e0211714 (2019)
Malaina, I., et al.: Metastasis of cutaneous melanoma: risk factors, detection and forecasting. In: Rojas, I., Ortuño, F. (eds.) IWBBIO 2018. LNCS, vol. 10813, pp. 511â519. Springer, Cham (2018). https://doi.org/10.1007/978-3-319-78723-7_44
Miller, A.J., Mihm, M.C.: Melanoma. N. Engl. J. Med. 355, 51â65 (2006)
Thompson, J.A.: The revised american joint committee on cancer staging system for melanoma. In: Seminars in Oncology, vol. 29, pp. 361â369. WB Saunders (2002)
Edlundh-Rose, E., et al.: NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res. 16, 471â478 (2006)
Nikolaev, S.I., et al.: Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nat. Genet. 44, 133 (2012)
Ott, P.A., et al.: An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547, 217 (2017)
Mann, E.R., Li, X.: Intestinal antigen-presenting cells in mucosal immune homeostasis: crosstalk between dendritic cells, macrophages and B-cells. World J. Gastroenterol. WJG 20, 9653 (2014)
Trolle, T., et al.: The length distribution of class Iârestricted T cell epitopes is determined by both peptide supply and MHC alleleâspecific binding preference. J. Immunol. 196, 1480â1487 (2016)
LĂłpez-MartĂnez, A., ChĂĄvez-Muñoz, C., Granados, J.: FunciĂłn biolĂłgica del complejo principal de histocompatibilidad. Revista de investigaciĂłn clĂnica 57, 132â141 (2005)
Sette, A., et al.: The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J. Immunol. 153, 5586â5592 (1994)
Moutaftsi, M., et al.: A consensus epitope prediction approach identifies the breadth of murine T CD8â+â-cell responses to vaccinia virus. Nat. Biotechnol. 24, 817 (2006)
Kotturi, M.F., et al.: The CD8+ T-cell response to lymphocytic choriomeningitis virus involves the L antigen: uncovering new tricks for an old virus. J. Virol. 81, 4928â4940 (2007)
Acknowledgements
This work was supported by Basque Government funding (IT1974-16, KK-2018/00090), and by the UPV/EHU and Basque Center of Applied Mathematics (US18/21)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this paper
Cite this paper
Malaina, I., Legarreta, L., Boyano, M.D., Alonso, S., De la Fuente, I.M., Martinez, L. (2020). Analyzing the Immune Response of Neoepitopes for Personalized Vaccine Design. In: Rojas, I., Valenzuela, O., Rojas, F., Herrera, L., Ortuño, F. (eds) Bioinformatics and Biomedical Engineering. IWBBIO 2020. Lecture Notes in Computer Science(), vol 12108. Springer, Cham. https://doi.org/10.1007/978-3-030-45385-5_4
Download citation
DOI: https://doi.org/10.1007/978-3-030-45385-5_4
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-45384-8
Online ISBN: 978-3-030-45385-5
eBook Packages: Computer ScienceComputer Science (R0)