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Identification and Targeting of Mutant Peptide Neoantigens in Cancer Immunotherapy

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journal contribution
posted on 22.09.2021, 00:52 by DJ Verdon, Misty JenkinsMisty Jenkins
In recent decades, adoptive cell transfer and checkpoint blockade therapies have revolutionized immunotherapeutic approaches to cancer treatment. Advances in whole exome/genome sequencing and bioinformatic detection of tumour-specific genetic variations and the amino acid sequence alterations they induce have revealed that T cell mediated anti-tumour immunity is substantially directed at mutated peptide sequences, and the identification and therapeutic targeting of patient-specific mutated peptide antigens now represents an exciting and rapidly progressing frontier of personalized medicine in the treatment of cancer. This review outlines the historical identification and validation of mutated peptide neoantigens as a target of the immune system, and the technical development of bioinformatic and experimental strategies for detecting, confirming and prioritizing both patient-specific or “private” and frequently occurring, shared “public” neoantigenic targets. Further, we examine the range of therapeutic modalities that have demonstrated preclinical and clinical anti-tumour efficacy through specifically targeting neoantigens, including adoptive T cell transfer, checkpoint blockade and neoantigen vaccination.

Funding

The authors would like to acknowledge the support of theWalter and Eliza Hall Institute of Medical Research. M.R.J. is funded by NHMRC, The Walter and Eliza Hall Institute of Medical Research Suzanne Cory Fellowship, RCD Foundation and Cancer Australia.

History

Publication Date

23/08/2021

Journal

Cancers

Volume

13

Issue

16

Article Number

4245

Pagination

20p.

Publisher

MDPI

ISSN

2072-6694

Rights Statement

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