Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells

Teresa R. Wagner; Simone Blaess; Inga B. Leske; Desiree I. Frecot; Marius Gramlich; Bjoern Traenkle; Philipp D. Kaiser; Dominik Seyfried; Sandra Maier; Amélie Rezza; Fabiane Sônego; Kader Thiam; Stefania Pezzana; Anne Zeck; Cécile Gouttefangeas; Armin M. Scholz; Stefan Nueske; Andreas Maurer; Manfred Kneilling; Bernd J. Pichler; Dominik Sonanini; Ulrich Rothbauer

doi:10.3389/fimmu.2023.1264179

Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells

Teresa R. Wagner, Simone Blaess, Inga B. Leske, Desiree I. Frecot, Marius Gramlich, Bjoern Traenkle, Philipp D. Kaiser, Dominik Seyfried, Sandra Maier, Amélie Rezza, Fabiane Sônego, Kader Thiam, Stefania Pezzana, Anne Zeck, Cécile Gouttefangeas, Armin M. Scholz, Stefan Nueske, Andreas Maurer, Manfred Kneilling, Bernd J. PichlerDominik Sonanini, Ulrich Rothbauer

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

2 Scopus citations

Abstract

Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the “don’t eat me” ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)–specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis. For non-invasive in vivo imaging, we chose S36 Nb as a non-modulating binder. By quantitative positron emission tomography in novel hSIRPα/hCD47 knock-in mice, we demonstrated the applicability of ⁶⁴Cu-hSIRPα-S36 Nb to visualize tumor infiltration of myeloid cells. We envision that the hSIRPα-Nbs presented in this study have potential as versatile theranostic probes, including novel myeloid-specific checkpoint inhibitors for combinatorial treatment approaches and for in vivo stratification and monitoring of individual responses during cancer immunotherapies.

Original language	English
Article number	1264179
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1264179
State	Published - 2023
Externally published	Yes

Keywords

PET imaging tracer
SIRPalpha
immune checkpoint inhibitor (ICI)
myeloid cells
nanobodies (Nbs)
theranostics

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10.3389/fimmu.2023.1264179

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Wagner, T. R., Blaess, S., Leske, I. B., Frecot, D. I., Gramlich, M., Traenkle, B., Kaiser, P. D., Seyfried, D., Maier, S., Rezza, A., Sônego, F., Thiam, K., Pezzana, S., Zeck, A., Gouttefangeas, C., Scholz, A. M., Nueske, S., Maurer, A., Kneilling, M., ... Rothbauer, U. (2023). Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells. Frontiers in Immunology, 14, Article 1264179. https://doi.org/10.3389/fimmu.2023.1264179

@article{e37af86044ad44f7a9303adb807fca12,

title = "Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells",

abstract = "Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the “don{\textquoteright}t eat me” ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)–specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis. For non-invasive in vivo imaging, we chose S36 Nb as a non-modulating binder. By quantitative positron emission tomography in novel hSIRPα/hCD47 knock-in mice, we demonstrated the applicability of 64Cu-hSIRPα-S36 Nb to visualize tumor infiltration of myeloid cells. We envision that the hSIRPα-Nbs presented in this study have potential as versatile theranostic probes, including novel myeloid-specific checkpoint inhibitors for combinatorial treatment approaches and for in vivo stratification and monitoring of individual responses during cancer immunotherapies.",

keywords = "PET imaging tracer, SIRPalpha, immune checkpoint inhibitor (ICI), myeloid cells, nanobodies (Nbs), theranostics",

author = "Wagner, {Teresa R.} and Simone Blaess and Leske, {Inga B.} and Frecot, {Desiree I.} and Marius Gramlich and Bjoern Traenkle and Kaiser, {Philipp D.} and Dominik Seyfried and Sandra Maier and Am{\'e}lie Rezza and Fabiane S{\^o}nego and Kader Thiam and Stefania Pezzana and Anne Zeck and C{\'e}cile Gouttefangeas and Scholz, {Armin M.} and Stefan Nueske and Andreas Maurer and Manfred Kneilling and Pichler, {Bernd J.} and Dominik Sonanini and Ulrich Rothbauer",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Wagner, Blaess, Leske, Frecot, Gramlich, Traenkle, Kaiser, Seyfried, Maier, Rezza, S{\^o}nego, Thiam, Pezzana, Zeck, Gouttefangeas, Scholz, Nueske, Maurer, Kneilling, Pichler, Sonanini and Rothbauer.",

year = "2023",

doi = "10.3389/fimmu.2023.1264179",

language = "English",

volume = "14",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

}

Wagner, TR, Blaess, S, Leske, IB, Frecot, DI, Gramlich, M, Traenkle, B, Kaiser, PD, Seyfried, D, Maier, S, Rezza, A, Sônego, F, Thiam, K, Pezzana, S, Zeck, A, Gouttefangeas, C, Scholz, AM, Nueske, S, Maurer, A, Kneilling, M, Pichler, BJ, Sonanini, D & Rothbauer, U 2023, 'Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells', Frontiers in Immunology, vol. 14, 1264179. https://doi.org/10.3389/fimmu.2023.1264179

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T1 - Two birds with one stone

T2 - human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells

AU - Wagner, Teresa R.

AU - Blaess, Simone

AU - Leske, Inga B.

AU - Frecot, Desiree I.

AU - Gramlich, Marius

AU - Traenkle, Bjoern

AU - Kaiser, Philipp D.

AU - Seyfried, Dominik

AU - Maier, Sandra

AU - Rezza, Amélie

AU - Sônego, Fabiane

AU - Thiam, Kader

AU - Pezzana, Stefania

AU - Zeck, Anne

AU - Gouttefangeas, Cécile

AU - Scholz, Armin M.

AU - Nueske, Stefan

AU - Maurer, Andreas

AU - Kneilling, Manfred

AU - Pichler, Bernd J.

AU - Sonanini, Dominik

AU - Rothbauer, Ulrich

N1 - Publisher Copyright: Copyright © 2023 Wagner, Blaess, Leske, Frecot, Gramlich, Traenkle, Kaiser, Seyfried, Maier, Rezza, Sônego, Thiam, Pezzana, Zeck, Gouttefangeas, Scholz, Nueske, Maurer, Kneilling, Pichler, Sonanini and Rothbauer.

PY - 2023

Y1 - 2023

N2 - Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the “don’t eat me” ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)–specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis. For non-invasive in vivo imaging, we chose S36 Nb as a non-modulating binder. By quantitative positron emission tomography in novel hSIRPα/hCD47 knock-in mice, we demonstrated the applicability of 64Cu-hSIRPα-S36 Nb to visualize tumor infiltration of myeloid cells. We envision that the hSIRPα-Nbs presented in this study have potential as versatile theranostic probes, including novel myeloid-specific checkpoint inhibitors for combinatorial treatment approaches and for in vivo stratification and monitoring of individual responses during cancer immunotherapies.

AB - Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the “don’t eat me” ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)–specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis. For non-invasive in vivo imaging, we chose S36 Nb as a non-modulating binder. By quantitative positron emission tomography in novel hSIRPα/hCD47 knock-in mice, we demonstrated the applicability of 64Cu-hSIRPα-S36 Nb to visualize tumor infiltration of myeloid cells. We envision that the hSIRPα-Nbs presented in this study have potential as versatile theranostic probes, including novel myeloid-specific checkpoint inhibitors for combinatorial treatment approaches and for in vivo stratification and monitoring of individual responses during cancer immunotherapies.

KW - PET imaging tracer

KW - SIRPalpha

KW - immune checkpoint inhibitor (ICI)

KW - myeloid cells

KW - nanobodies (Nbs)

KW - theranostics

UR - http://www.scopus.com/inward/record.url?scp=85181198162&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2023.1264179

DO - 10.3389/fimmu.2023.1264179

M3 - Article

C2 - 38164132

AN - SCOPUS:85181198162

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1264179

ER -

Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells

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Keywords

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