Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens

Chiara M. Cattaneo; Thomas Battaglia; Jos Urbanus; Ziva Moravec; Rhianne Voogd; Rosa de Groot; Koen J. Hartemink; John B. A. G. Haanen; Emile E. Voest; Ton N. Schumacher; Wouter Scheper

doi:https://doi.org/10.1038/s41587-022-01547-0

Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens

Chiara M. Cattaneo, Thomas Battaglia, Jos Urbanus, Ziva Moravec, Rhianne Voogd, Rosa de Groot, Koen J. Hartemink, John B. A. G. Haanen, Emile E. Voest, Ton N. Schumacher, Wouter Scheper

Research output: Contribution to journal › Article › Academic › peer-review

9 Citations (Scopus)

Abstract

Cancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of neoantigen repertoires that can be uncovered. Here, we develop a genetic neoantigen screening system that allows sensitive identification of CD4+ and CD8+ T cell-recognized neoantigens across patients’ complete HLA genotypes.

Original language	English
Pages (from-to)	783-787
Number of pages	5
Journal	Nature biotechnology
Volume	41
Issue number	6
Early online date	2023
DOIs	https://doi.org/10.1038/s41587-022-01547-0
Publication status	Published - Jun 2023

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@article{0ed54a22b9644eeea1a15ce8000ca997,

title = "Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens",

abstract = "Cancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of neoantigen repertoires that can be uncovered. Here, we develop a genetic neoantigen screening system that allows sensitive identification of CD4+ and CD8+ T cell-recognized neoantigens across patients{\textquoteright} complete HLA genotypes.",

author = "Cattaneo, {Chiara M.} and Thomas Battaglia and Jos Urbanus and Ziva Moravec and Rhianne Voogd and {de Groot}, Rosa and Hartemink, {Koen J.} and Haanen, {John B. A. G.} and Voest, {Emile E.} and Schumacher, {Ton N.} and Wouter Scheper",

note = "Funding Information: We would like to thank M. Slagter and L. Wessels for bioinformatic and statistical support, K. Dijkstra for support with single-cell TCR sequencing, A. van de Leun for support with isolation of neoantigen-specific TCRs, M. Wolkers for kindly sharing patient material, K. Bresser and D. Vredevoogd for helpful discussions on library design, the NKI-AVL Flow Cytometry Facility for flow cytometric support, the NKI-AVL Core Facility Molecular Pathology and Biobanking for supplying NKI-AVL Biobank material and laboratory support and the NKI-AVL Genomics Core Facility for support with next-generation sequencing. This work was supported by the Dutch Cancer Society Young Investigator Grant (grant No. 2020-1/12977) (to W.S.), ZonMw Translational Research Program 2 (grant No. 446002001) (to W.S. and J.B.A.G.H.), the Queen Wilhelmina Cancer Research Award and ERC AdG SENSIT (grant agreement No. 742259) (to T.N.S.), the NWO Gravitation program (NWO 2012-2022) (to E.E.V.) and Oncode Institute (to T.N.S. and E.E.V.). Figure 1a was created with BioRender.com. Funding Information: T.N.S. is advisor for Allogene Therapeutics, Celsius, Merus, Neogene Therapeutics and Scenic Biotech; is a recipient of research support from Merck KgaA; is a stockholder in Allogene Therapeutics, Cell Control, Celsius, Merus, Neogene Therapeutics and Scenic Biotech and is venture partner at Third Rock Ventures, all outside of the current work. J.B.A.G.H. is advisor for BioNTech, Neogene Therapeutics, Scenic Biotech and T-Knife; is a recipient of research grant support from BioNTech; is a stock option holder in Neogene Therapeutics, all outside of the current work. All other authors declare no competing interests. Funding Information: We would like to thank M. Slagter and L. Wessels for bioinformatic and statistical support, K. Dijkstra for support with single-cell TCR sequencing, A. van de Leun for support with isolation of neoantigen-specific TCRs, M. Wolkers for kindly sharing patient material, K. Bresser and D. Vredevoogd for helpful discussions on library design, the NKI-AVL Flow Cytometry Facility for flow cytometric support, the NKI-AVL Core Facility Molecular Pathology and Biobanking for supplying NKI-AVL Biobank material and laboratory support and the NKI-AVL Genomics Core Facility for support with next-generation sequencing. This work was supported by the Dutch Cancer Society Young Investigator Grant (grant No. 2020-1/12977) (to W.S.), ZonMw Translational Research Program 2 (grant No. 446002001) (to W.S. and J.B.A.G.H.), the Queen Wilhelmina Cancer Research Award and ERC AdG SENSIT (grant agreement No. 742259) (to T.N.S.), the NWO Gravitation program (NWO 2012-2022) (to E.E.V.) and Oncode Institute (to T.N.S. and E.E.V.). Figure was created with BioRender.com . Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = jun,

doi = "https://doi.org/10.1038/s41587-022-01547-0",

language = "English",

volume = "41",

pages = "783--787",

journal = "Nature biotechnology",

issn = "1087-0156",

publisher = "Nature Publishing Group",

number = "6",

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TY - JOUR

T1 - Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens

AU - Cattaneo, Chiara M.

AU - Battaglia, Thomas

AU - Urbanus, Jos

AU - Moravec, Ziva

AU - Voogd, Rhianne

AU - de Groot, Rosa

AU - Hartemink, Koen J.

AU - Haanen, John B. A. G.

AU - Voest, Emile E.

AU - Schumacher, Ton N.

AU - Scheper, Wouter

N1 - Funding Information: We would like to thank M. Slagter and L. Wessels for bioinformatic and statistical support, K. Dijkstra for support with single-cell TCR sequencing, A. van de Leun for support with isolation of neoantigen-specific TCRs, M. Wolkers for kindly sharing patient material, K. Bresser and D. Vredevoogd for helpful discussions on library design, the NKI-AVL Flow Cytometry Facility for flow cytometric support, the NKI-AVL Core Facility Molecular Pathology and Biobanking for supplying NKI-AVL Biobank material and laboratory support and the NKI-AVL Genomics Core Facility for support with next-generation sequencing. This work was supported by the Dutch Cancer Society Young Investigator Grant (grant No. 2020-1/12977) (to W.S.), ZonMw Translational Research Program 2 (grant No. 446002001) (to W.S. and J.B.A.G.H.), the Queen Wilhelmina Cancer Research Award and ERC AdG SENSIT (grant agreement No. 742259) (to T.N.S.), the NWO Gravitation program (NWO 2012-2022) (to E.E.V.) and Oncode Institute (to T.N.S. and E.E.V.). Figure 1a was created with BioRender.com. Funding Information: T.N.S. is advisor for Allogene Therapeutics, Celsius, Merus, Neogene Therapeutics and Scenic Biotech; is a recipient of research support from Merck KgaA; is a stockholder in Allogene Therapeutics, Cell Control, Celsius, Merus, Neogene Therapeutics and Scenic Biotech and is venture partner at Third Rock Ventures, all outside of the current work. J.B.A.G.H. is advisor for BioNTech, Neogene Therapeutics, Scenic Biotech and T-Knife; is a recipient of research grant support from BioNTech; is a stock option holder in Neogene Therapeutics, all outside of the current work. All other authors declare no competing interests. Funding Information: We would like to thank M. Slagter and L. Wessels for bioinformatic and statistical support, K. Dijkstra for support with single-cell TCR sequencing, A. van de Leun for support with isolation of neoantigen-specific TCRs, M. Wolkers for kindly sharing patient material, K. Bresser and D. Vredevoogd for helpful discussions on library design, the NKI-AVL Flow Cytometry Facility for flow cytometric support, the NKI-AVL Core Facility Molecular Pathology and Biobanking for supplying NKI-AVL Biobank material and laboratory support and the NKI-AVL Genomics Core Facility for support with next-generation sequencing. This work was supported by the Dutch Cancer Society Young Investigator Grant (grant No. 2020-1/12977) (to W.S.), ZonMw Translational Research Program 2 (grant No. 446002001) (to W.S. and J.B.A.G.H.), the Queen Wilhelmina Cancer Research Award and ERC AdG SENSIT (grant agreement No. 742259) (to T.N.S.), the NWO Gravitation program (NWO 2012-2022) (to E.E.V.) and Oncode Institute (to T.N.S. and E.E.V.). Figure was created with BioRender.com . Publisher Copyright: © 2023, The Author(s).

PY - 2023/6

Y1 - 2023/6

N2 - Cancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of neoantigen repertoires that can be uncovered. Here, we develop a genetic neoantigen screening system that allows sensitive identification of CD4+ and CD8+ T cell-recognized neoantigens across patients’ complete HLA genotypes.

AB - Cancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of neoantigen repertoires that can be uncovered. Here, we develop a genetic neoantigen screening system that allows sensitive identification of CD4+ and CD8+ T cell-recognized neoantigens across patients’ complete HLA genotypes.

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U2 - https://doi.org/10.1038/s41587-022-01547-0

DO - https://doi.org/10.1038/s41587-022-01547-0

M3 - Article

C2 - 36593398

SN - 1087-0156

VL - 41

SP - 783

EP - 787

JO - Nature biotechnology

JF - Nature biotechnology

IS - 6

ER -

Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens

Abstract

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