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IMMUNOTHERAPY

Targeting the cancer mutanome of breast cancer

Nature Medicine volume 24, pages 703–704 (2018)Cite this article

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A metastatic hormone receptor–positive breast cancer, usually resistant to immunotherapy, is successfully treated with tumor-infiltrating lymphocytes enriched for neoantigen reactivity, underscoring the broad potential of this immunotherapeutic approach.

Mutations in cancer (the tumor ‘mutanome’) are the source of neoantigens that can be recognized by the immune system as foreign-like peptides called ‘neoepitopes’ presented on major histocompatibility complex (MHC) molecules1. Although the cancer mutanome is considered to be a possible source of potent tumor antigens for cancer immunotherapy, it remained largely out of reach for decades because of the lack of suitable genomic and proteomic methods to identify actionable mutations. Recent advances in genomic DNA and RNA sequencing as well as the improved software tools for discerning single-nucleotide variants (SNVs) and other relevant genomic alterations together with improved prediction of peptide sequence binding affinities to different subtypes of MHC molecules have made this elusive source of antigens actionable in a realistic and practical way2. A number of immunotherapeutic approaches, including vaccination with synthesized long peptides or RNA, DNA plasmid, or viral vector vaccines that encode relevant neoepitope sequences, as well as activated T cell therapies that recognize neoantigens, are now in development3.

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Fig. 1: Adoptive T cell therapy successfully treats a metastatic hormone receptor–positive breast cancer.

References

  1. Campbell, B. B. et al. Cell 171, 1042–1056.e1010 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Alvarez, B., Barra, C., Nielsen, M. & Andreatta, M. Proteomics https://doi.org/10.1002/pmic.201700252 (2018).

  3. Efremova, M., Finotello, F., Rieder, D. & Trajanoski, Z. Front. Immunol. 8, 1679 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dudley, M. E. et al. Science 298, 850–854 (2002).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Rosenberg, S. A. Nat. Rev. Clin. Oncol. 8, 577–585 (2011).

    Article  PubMed  CAS  Google Scholar 

  6. Goodman, A. M. et al. Mol. Cancer Ther. 16, 2598–2608 (2017).

    Article  PubMed  CAS  Google Scholar 

  7. Schumacher, T. N. & Hacohen, N. Curr. Opin. Immunol. 41, 98–103 (2016).

    Article  PubMed  CAS  Google Scholar 

  8. Zacharakis, N. et al. Nat. Med. https://doi.org/10.1038/s41591-018-0040-8 (2018).

  9. Bobisse, S. et al. Nat. Commun. 9, 1092 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Robbins, P. F. et al. Nat. Med. 19, 747–752 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Kreiter, S. et al. Nature 520, 692–696 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Chowell, D. et al. Science 359, 582–587 (2018).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The author thanks all colleagues and scientists who over the years have shared ideas and concepts and have worked diligently to develop cell therapy and vaccination for cancer, bringing it to the forefront of immunotherapy.

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  1. Ontario Institute for Cancer Research, Toronto, Ontario, Canada

    Laszlo G. Radvanyi

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  1. Laszlo G. Radvanyi
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Correspondence to Laszlo G. Radvanyi.

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Radvanyi, L.G. Targeting the cancer mutanome of breast cancer. Nat Med 24, 703–704 (2018). https://doi.org/10.1038/s41591-018-0065-z

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