The perfect personalized cancer therapy: cancer vaccines against neoantigens - PubMed (original) (raw)

Review

The perfect personalized cancer therapy: cancer vaccines against neoantigens

Luigi Aurisicchio et al. J Exp Clin Cancer Res. 2018.

Abstract

In the advent of Immune Checkpoint inhibitors (ICI) and of CAR-T adoptive T-cells, the new frontier in Oncology is Cancer Immunotherapy because of its ability to provide long term clinical benefit in metastatic disease in several solid and liquid tumor types. It is now clear that ICI acts by unmasking preexisting immune responses as well as by inducing de novo responses against tumor neoantigens. Thanks to theprogress made in genomics technologies and the evolution of bioinformatics, neoantigens represent ideal targets, due to their specific expression in cancer tissue and the potential lack of side effects. In this review, we discuss the promise of preclinical and clinical results with mutation-derived neoantigen cancer vaccines (NCVs) along with the current limitations from bioinformatics prediction to manufacturing an effective new therapeutic approach.

PubMed Disclaimer

Conflict of interest statement

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Fig. 1

The pipeline of neoantigen cancer vaccine production, for mouse studies (left side and human studies (right side). 1. Tumor and normal tissue are collected and subjected to (2) exome sequencing and RNAseq analysis for the tumor samples. 3. expressed non-synonymous mutations are then further selected according to binding to predictive algorithms and incorporated in a vaccine vector or delivered as peptides with adjuvants

Fig. 2

Fig. 2

Personalized NCV in the context of current immunotherapy, the three dimensions are defined by tumor infiltrating lymphocytes (TILs), mutational load (ML) and tumor heterogeneity (TH). Patients in the lower right panel (TIL−ML+TH+) may benefit from Neoantigen cancer vaccine (NCV) approach whereas patients in the upper right panel (TILs+ML+TH−) respond more to immune checkpoint inhibitors (ICI)

Similar articles

Cited by

References

    1. Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 2017;7:264–276. doi: 10.1158/2159-8290.CD-16-0828. - DOI - PMC - PubMed
    1. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjörd JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jäger N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, López-Otín C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdés-Mas R, van Buuren MM, van 't Veer L, Vincent-Salomon A, Waddell N, Yates LR; Australian Pancreatic Cancer Genome Initiative; ICGC Breast Cancer Consortium; ICGC MMML-Seq Consortium; ICGC PedBrain, Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21. 10.1038/nature12477. Epub 2013 Aug 14. Erratum in: Nature. 2013 Oct 10;502(7470):258. Imielinsk, Marcin [corrected to Imielinski, Marcin]. - PMC - PubMed
    1. Zhao B, Sedlak JC, Srinivas R, Creixell P, Pritchard JR, Tidor B, et al. Exploiting temporal collateral sensitivity in tumor clonal evolution. Cell Elsevier Inc. 2016;165:234–46. Available from: http://www.cell.com/cell/fulltext/S0092-8674(16)30059-9 - PMC - PubMed
    1. Seliger B, Kloor M, Ferrone S. HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance. Oncoimmunology. 2017;6(2):e1171447. 10.1080/2162402X.2016.1171447. - PMC - PubMed
    1. Hu Z, Ott PA, Wu CJ. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat. Publ. Gr. Nature Publishing Group; 2017; Available from: 10.1038/nri.2017.131 - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources