Relevance of mutation-derived neoantigens and non-classical antigens for anticancer therapies

ABSTRACT

Efficacy of cancer immunotherapies relies on correct recognition of tumor antigens by lymphocytes, eliciting thus functional responses capable of eliminating tumor cells. Therefore, important efforts have been carried out in antigen identification, with the aim of understanding mechanisms of response to immunotherapy and to design safer and more efficient strategies. In addition to classical tumor-associated antigens identified during the last decades, implementation of next-generation sequencing methodologies is enabling the identification of neoantigens (neoAgs) arising from mutations, leading to the development of new neoAg-directed therapies. Moreover, there are numerous non-classical tumor antigens originated from other sources and identified by new methodologies. Here, we review the relevance of neoAgs in different immunotherapies and the results obtained by applying neoAg-based strategies. In addition, the different types of non-classical tumor antigens and the best approaches for their identification are described. This will help to increase the spectrum of targetable molecules useful in cancer immunotherapies.

KEYWORDS:

• Tumor neoantigens
• mutations
• non-classical tumor antigens
• ribosome profiling
• immunopeptidomics

Acknowledgments

PF is supported by Gobierno de Navarra (0011-1411-2021-000070 and 0011‐1383‐2022‐ 000014 projects), RTI2018-101759-B-I00, PDC2022-133961-100 and PID2021-128791OB-I00 MCIN/AEI/10.13039/501100011033/FEDER, UE, Scientific Foundation of the Spanish Association Against Cancer (AECC IDEAS20169FORT to P.F.) and by the Instituto de Salud Carlos III, which finances Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd) and Red Española de Terapias Avanzadas TERAV ISCIII (RICORS: (RD21/0017), financed by the EU (NextGenerationEU. Plan de Recuperación Transformación y Resiliencia). PS is funded by Instituto de Salud Carlos III (ISCIII) through the project “PI20/00260” and co-funded by the European Union and FEDER and by Gobierno de Navarra (grants GNS_54-2021, 0011-1411-2020-000011 and 0011-1411-2020-000010). S.H.-S. is funded by ISCIII (PI21/00292) and Gobierno de Navarra (Dpto. de Salud -045-2017/HEPATIL), co-financed with “Fondos FEDER” (“Una manera de hacer Europa”), and Gobierno de Navarra (Dpto. Industria – GN2020 PC196-197/SOLIDET- and Proyectos Estrategicos de I+D 2023-2026-0011-1411-2023-000072/PITAGORAS).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by the Gobierno de Navarra [045-2017/HEPATIL]; Gobierno de Navarra [0011-1411-2020-000011]; Gobierno de Navarra [GNS_54-2021]; Gobierno de Navarra [0011‐1383‐2022‐ 000014]; Gobierno de Navarra [0011-1411-2021-000070]; Gobierno de Navarra [0011-1411-2023-000072/PITAGORAS]; Gobierno de Navarra [GN2020 PC196-197/SOLIDET]; Gobierno de Navarra [0011-1411-2020-000010]; Instituto de Salud Carlos III [PI20/00260]; Instituto de Salud Carlos III [CIBERejd TERAv]; Instituto de Salud Carlos III [PI21/00292]; Ministerio de Ciencia e Innovación [PID2021-128791OBI00 MCIN/AEI/10.13039/501100011033]; Ministerio de Ciencia e Innovación [PDC2022-133961-100]; Ministerio de Ciencia e Innovación [RTI2018-101759-B-I00]; Foundation of the Spanish Association Against Cancer [AECC IDEAS20169FORT].