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Publications

Recent publications Breckpot Group

A synthetic DNA template for fast manufacturing of versatile single epitope mRNA

26/09/2022

Mol Ther Nucleic Acids. 2022 Aug 17;29:943-954. doi: 10.1016/j.omtn.2022.08.021. eCollection 2022 Sep 13.

ABSTRACT

A flexible, affordable, and rapid vaccine platform is necessary to unlock the potential of personalized cancer vaccines in order to achieve full clinical efficiency...

mRNA-LNP vaccines tuned for systemic immunization induce strong antitumor immunity by engaging splenic immune cells

13/07/2022

Mol Ther. 2022 Sep 7;30(9):3078-3094. doi: 10.1016/j.ymthe.2022.07.007. Epub 2022 Jul 12.

ABSTRACT

mRNA vaccines have recently proved to be highly effective against SARS-CoV-2. Key to their success is the lipid-based nanoparticle (LNP), which enables efficient mRNA expression and...

Emerging applications of nanobodies in cancer therapy

01/07/2022

Int Rev Cell Mol Biol. 2022;369:143-199. doi: 10.1016/bs.ircmb.2022.03.010. Epub 2022 May 18.

ABSTRACT

Cancer is a heterogeneous disease, requiring treatment tailored to the unique phenotype of the patient's tumor. Monoclonal antibodies (mAbs) and variants thereof have enabled...

Inhibiting Histone and DNA Methylation Improves Cancer Vaccination in an Experimental Model of Melanoma

31/05/2022

Front Immunol. 2022 May 12;13:799636. doi: 10.3389/fimmu.2022.799636. eCollection 2022.

ABSTRACT

Immunotherapy has improved the treatment of malignant skin cancer of the melanoma type, yet overall clinical response rates remain low. Combination therapies could be key to meet this...

RNA in Cancer Immunotherapy: Unlocking the Potential of the Immune System

18/05/2022

Clin Cancer Res. 2022 Sep 15;28(18):3929-3939. doi: 10.1158/1078-0432.CCR-21-3304.

ABSTRACT

Recent advances in the manufacturing, modification, purification, and cellular delivery of ribonucleic acid (RNA) have enabled the development of RNA-based therapeutics for a broad array...

Oncolytic Herpes Simplex Virus Type 1 Induces Immunogenic Cell Death Resulting in Maturation of BDCA-1<sup>+</sup> Myeloid Dendritic Cells

14/05/2022

Int J Mol Sci. 2022 Apr 27;23(9):4865. doi: 10.3390/ijms23094865.

ABSTRACT

Recently, a paradigm shift has been established for oncolytic viruses (OVs) as it was shown that the immune system plays an important role in the specific killing of tumor cells by OVs. OVs have the...

Targeted Radionuclide Therapy with Low and High-Dose Lutetium-177-Labeled Single Domain Antibodies Induces Distinct Immune Signatures in a Mouse Melanoma Model

02/05/2022

Mol Cancer Ther. 2022 Jul 5;21(7):1136-1148. doi: 10.1158/1535-7163.MCT-21-0791.

ABSTRACT

Targeted radionuclide therapy (TRT) using probes labeled with Lutetium-177 (177Lu) represents a new and growing type of cancer therapy. We studied immunologic changes in response to TRT with...

TNF-α-Secreting Lung Tumor-Infiltrated Monocytes Play a Pivotal Role During Anti-PD-L1 Immunotherapy

02/05/2022

Front Immunol. 2022 Apr 14;13:811867. doi: 10.3389/fimmu.2022.811867. eCollection 2022.

ABSTRACT

Immune checkpoint blockade (ICB) of the PD-1 pathway revolutionized the survival forecast for advanced non-small cell lung cancer (NSCLC). Yet, the majority of PD-L1 + NSCLC patients...

Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring

28/02/2022

Front Immunol. 2022 Feb 11;13:794175. doi: 10.3389/fimmu.2022.794175. eCollection 2022.

ABSTRACT

Scoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2 + and triple-negative...

CS1-specific single-domain antibodies labeled with Actinium-225 prolong survival and increase CD8+ T cells and PD-L1 expression in Multiple Myeloma

15/11/2021

Oncoimmunology. 2021 Nov 9;10(1):2000699. doi: 10.1080/2162402X.2021.2000699. eCollection 2021.

ABSTRACT

Multiple myeloma (MM) is a hematological malignancy characterized by the presence of clonal plasma cells in the bone marrow niche. Despite significant therapeutic advances, MM...

Unraveling the Effects of a Talimogene Laherparepvec (T-VEC)-Induced Tumor Oncolysate on Myeloid Dendritic Cells

15/11/2021

Front Immunol. 2021 Oct 28;12:733506. doi: 10.3389/fimmu.2021.733506. eCollection 2021.

ABSTRACT

T-VEC, a HSV-1 derived oncolytic virus, is approved for the treatment of advanced melanoma. The mechanisms that underly the systemic anti-tumor effect that is seen following...

T-cell subsets in the skin and their role in inflammatory skin disorders

24/09/2021

Allergy. 2022 Mar;77(3):827-842. doi: 10.1111/all.15104. Epub 2021 Oct 6.

ABSTRACT

T lymphocytes (T cells) are major players of the adaptive immune response. Naive T cells are primed in the presence of cytokines, leading to polarization into distinct T-cell subsets with specific...

Formatting and gene-based delivery of a human PD-L1 single domain antibody for immune checkpoint blockade

06/09/2021

Mol Ther Methods Clin Dev. 2021 Jun 4;22:172-182. doi: 10.1016/j.omtm.2021.05.017. eCollection 2021 Sep 10.

ABSTRACT

Monoclonal antibodies that target the inhibitory immune checkpoint axis consisting of programmed cell death protein 1 (PD-1) and its ligand, PD-L1, have changed...

Site-Specific Radiolabeling of a Human PD-L1 Nanobody via Maleimide-Cysteine Chemistry

02/07/2021

Pharmaceuticals (Basel). 2021 Jun 8;14(6):550. doi: 10.3390/ph14060550.

ABSTRACT

Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) and its ligand PD-L1 have proven to be efficient cancer therapies in a subset of patients. From all the patients with various...

The antigen-binding moiety in the driver's seat of CARs

24/05/2021

Med Res Rev. 2022 Jan;42(1):306-342. doi: 10.1002/med.21818. Epub 2021 May 24.

ABSTRACT

Immuno-oncology has been at the forefront of cancer treatment in recent decades. In particular immune checkpoint and chimeric antigen receptor (CAR)-T cell therapy have achieved spectacular...

Recent publication Movahedi Group

Single-cell RNA and protein profiling of immune cells from the mouse brain and its border tissues

05/08/2022

Nat Protoc. 2022 Oct;17(10):2354-2388. doi: 10.1038/s41596-022-00716-4. Epub 2022 Aug 5.

ABSTRACT

Brain-immune cross-talk and neuroinflammation critically shape brain physiology in health and disease. A detailed understanding of the brain immune landscape is essential for...

Macrophage compartmentalization in the brain and cerebrospinal fluid system

04/03/2022

Sci Immunol. 2022 Mar 4;7(69):eabk0391. doi: 10.1126/sciimmunol.abk0391. Epub 2022 Mar 4.

ABSTRACT

Macrophages reside within the diverse anatomical compartments of the central nervous system (CNS). Within each compartment, these phagocytes are exposed to unique combinations of...

Comparative analysis of antibody- and lipid-based multiplexing methods for single-cell RNA-seq

17/02/2022

Genome Biol. 2022 Feb 16;23(1):55. doi: 10.1186/s13059-022-02628-8.

ABSTRACT

BACKGROUND: Multiplexing of samples in single-cell RNA-seq studies allows a significant reduction of the experimental costs, straightforward identification of doublets, increased cell throughput, and...

Imaging of Glioblastoma Tumor-Associated Myeloid Cells Using Nanobodies Targeting Signal Regulatory Protein Alpha

17/12/2021

Front Immunol. 2021 Nov 30;12:777524. doi: 10.3389/fimmu.2021.777524. eCollection 2021.

ABSTRACT

Glioblastoma (GBM) is the most common malignant primary brain tumor. Glioblastomas contain a large non-cancerous stromal compartment including various populations of tumor-associated...

MMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System

07/08/2021

Cells. 2021 Jul 2;10(7):1672. doi: 10.3390/cells10071672.

ABSTRACT

Neuroinflammation has been put forward as a mechanism triggering axonal regrowth in the mammalian central nervous system (CNS), yet little is known about the underlying cellular and molecular players connecting...

CSF1R inhibition rescues tau pathology and neurodegeneration in an A/T/N model with combined AD pathologies, while preserving plaque associated microglia

09/06/2021

Acta Neuropathol Commun. 2021 Jun 8;9(1):108. doi: 10.1186/s40478-021-01204-8.

ABSTRACT

Alzheimer's disease (AD) is characterized by a sequential progression of amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N), constituting ATN pathology. While microglia...

Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies

24/05/2021

Adv Sci (Weinh). 2021 Mar 8;8(10):2004574. doi: 10.1002/advs.202004574. eCollection 2021 May.

ABSTRACT

Tumor-associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of...

Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization

30/03/2021

Nat Neurosci. 2021 Apr;24(4):595-610. doi: 10.1038/s41593-020-00789-y. Epub 2021 Mar 29.

ABSTRACT

Glioblastomas are aggressive primary brain cancers that recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease...

Therapeutic depletion of CCR8<sup>+</sup> tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy

16/02/2021

J Immunother Cancer. 2021 Feb;9(2):e001749. doi: 10.1136/jitc-2020-001749.

ABSTRACT

BACKGROUND: Modulation and depletion strategies of regulatory T cells (Tregs) constitute valid approaches in antitumor immunotherapy but suffer from severe adverse effects due to their lack of...

Monocytic myeloid-derived suppressor cells home to tumor-draining lymph nodes via CCR2 and locally modulate the immune response

08/02/2021

Cell Immunol. 2021 Apr;362:104296. doi: 10.1016/j.cellimm.2021.104296. Epub 2021 Jan 30.

ABSTRACT

Efficient priming of anti-tumor T cells requires the uptake and presentation of tumor antigens by immunogenic dendritic cells (DCs) and occurs mainly in lymph nodes draining the...

A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages

17/12/2020

Immunity. 2021 Jan 12;54(1):176-190.e7. doi: 10.1016/j.immuni.2020.11.007. Epub 2020 Dec 16.

ABSTRACT

The developmental and molecular heterogeneity of tissue macrophages is unravelling, as are their diverse contributions to physiology and pathophysiology. Moreover, also given...

Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge

13/10/2020

Immunity. 2020 Nov 17;53(5):1033-1049.e7. doi: 10.1016/j.immuni.2020.09.018. Epub 2020 Oct 12.

ABSTRACT

Microglia, the resident macrophages of the brain parenchyma, are key players in central nervous system (CNS) development, homeostasis, and disorders. Distinct brain pathologies...

Tightening the retinal glia limitans attenuates neuroinflammation after optic nerve injury

10/07/2020

Glia. 2020 Dec;68(12):2643-2660. doi: 10.1002/glia.23875. Epub 2020 Jul 9.

ABSTRACT

Increasing evidence suggests that functional impairments at the level of the neurovascular unit (NVU) underlie many neurodegenerative and neuroinflammatory diseases. While being part of the NVU,...

Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies

05/02/2020

Elife. 2020 Feb 4;9:e52176. doi: 10.7554/eLife.52176.

ABSTRACT

Cancer immunotherapy by immune checkpoint blockade has proven its great potential by saving the lives of a proportion of late stage patients with immunogenic tumor types. However, even in these sensitive tumor types,...

Identifying the variables that drive tamoxifen-independent CreERT2 recombination: Implications for microglial fate mapping and gene deletions

01/12/2019

Eur J Immunol. 2020 Mar;50(3):459-463. doi: 10.1002/eji.201948162. Epub 2019 Dec 11.

ABSTRACT

Ligand-dependent Cre recombinases such as the CreERT2 system allow for tamoxifen-inducible Cre recombination. Important examples are the Cx3cr1-CreERT2 and Sall1-CreERT2 lines that are...

Stromal-targeting radioimmunotherapy mitigates the progression of therapy-resistant tumors

19/10/2019

J Control Release. 2019 Nov 28;314:1-11. doi: 10.1016/j.jconrel.2019.10.024. Epub 2019 Oct 15.

ABSTRACT

Radioimmunotherapy (RIT) aims to deliver a high radiation dose to cancer cells, while minimizing the exposure of normal cells. Typically, monoclonal antibodies are used to...

A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment

08/05/2019

Nat Neurosci. 2019 Jun;22(6):1021-1035. doi: 10.1038/s41593-019-0393-4. Epub 2019 May 6.

ABSTRACT

While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border...

Single-domain antibody fusion proteins can target and shuttle functional proteins into macrophage mannose receptor expressing macrophages

25/02/2019

J Control Release. 2019 Apr 10;299:107-120. doi: 10.1016/j.jconrel.2019.02.023. Epub 2019 Feb 21.

ABSTRACT

The tumor microenvironment of numerous prevalent cancer types is abundantly infiltrated with tumor-associated macrophages (TAMs). Macrophage mannose receptor (MMR or CD206)...

Clinical Translation of [<sup>68</sup>Ga]Ga-NOTA-anti-MMR-sdAb for PET/CT Imaging of Protumorigenic Macrophages

24/01/2019

Mol Imaging Biol. 2019 Oct;21(5):898-906. doi: 10.1007/s11307-018-01302-5.

ABSTRACT

PURPOSE: Macrophage mannose receptor (MMR, CD206) expressing tumor-associated macrophages (TAM) are protumorigenic and was reported to negatively impact therapy responsiveness and is associated...

Targeting Protumoral Tumor-Associated Macrophages with Nanobody-Functionalized Nanogels through Strain Promoted Azide Alkyne Cycloaddition Ligation

12/06/2018

Bioconjug Chem. 2018 Jul 18;29(7):2394-2405. doi: 10.1021/acs.bioconjchem.8b00319. Epub 2018 Jun 28.

ABSTRACT

Tumor-associated macrophages (TAMs) with high expression levels of the Macrophage Mannose Receptor (MMR, CD206) exhibit a strong angiogenic and immune suppressive...

Endothelial C-Type Natriuretic Peptide Acts on Pericytes to Regulate Microcirculatory Flow and Blood Pressure

08/04/2018

Circulation. 2018 Jul 31;138(5):494-508. doi: 10.1161/CIRCULATIONAHA.117.033383.

ABSTRACT

BACKGROUND: Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular...

RoMo: An efficient strategy for functional mosaic analysis via stochastic Cre recombination and gene targeting in the ROSA26 locus

25/03/2018

Biotechnol Bioeng. 2018 Jul;115(7):1778-1792. doi: 10.1002/bit.26594. Epub 2018 Mar 31.

ABSTRACT

Functional mosaic analysis allows for the direct comparison of mutant cells with differentially marked control cells in the same organism. While this offers a powerful approach for...

Myeloid cell heterogeneity in cancer: not a single cell alike

28/02/2018

Cell Immunol. 2018 Aug;330:188-201. doi: 10.1016/j.cellimm.2018.02.008. Epub 2018 Feb 14.

ABSTRACT

Tumors of various histological origins show abundant infiltration of myeloid cells from early stages of disease progression. These cells have a profound impact on antitumor immunity...

Beyond the M-CSF receptor - novel therapeutic targets in tumor-associated macrophages

24/08/2017

FEBS J. 2018 Feb;285(4):777-787. doi: 10.1111/febs.14202. Epub 2017 Sep 6.

ABSTRACT

Tumor-associated macrophages (TAM) are by now established as important regulators of tumor progression by impacting on tumor immunity, angiogenesis, and metastasis. Hence, a multitude of...

Novel insights in the regulation and function of macrophages in the tumor microenvironment

30/10/2016

Curr Opin Oncol. 2017 Jan;29(1):55-61. doi: 10.1097/CCO.0000000000000344.

ABSTRACT

PURPOSE OF REVIEW: Tumors contain not only cancer cells but also nontransformed types of cells, the stromal cells. A bidirectional interplay exists between transformed and nontransformed cells...

Odorant receptors can mediate axonal identity and gene choice via cAMP-independent mechanisms

29/07/2016

Open Biol. 2016 Jul;6(7):160018. doi: 10.1098/rsob.160018.

ABSTRACT

Odorant receptors (ORs) control several aspects of cell fate in olfactory sensory neurons (OSNs), including singular gene choice and axonal identity. The mechanisms of OR-induced axon guidance have been suggested...

The Ontogeny and Microenvironmental Regulation of Tumor-Associated Macrophages

30/03/2016

Antioxid Redox Signal. 2016 Nov 10;25(14):775-791. doi: 10.1089/ars.2016.6704. Epub 2016 May 17.

ABSTRACT

SIGNIFICANCE: Tumor progression is supported by non-cancerous stromal cells, of which tumor-associated macrophages (TAMs) are prominent constituents. These cells could be...

Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment

07/07/2015

Biochim Biophys Acta. 2016 Jan;1865(1):23-34. doi: 10.1016/j.bbcan.2015.06.009. Epub 2015 Jul 2.

ABSTRACT

The tumor-promoting role of macrophages has been firmly established in most cancer types. However, macrophage identity has been a matter of debate, since several levels of...

Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population

14/11/2013

Cancer Res. 2014 Jan 1;74(1):24-30. doi: 10.1158/0008-5472.CAN-13-1196. Epub 2013 Nov 12.

ABSTRACT

Tumor-associated macrophages (TAM) are exposed to multiple microenvironmental cues in tumors, which collaborate to endow these cells with protumoral activities. Hypoxia, caused by...

Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T-cell activation events

24/07/2013

Eur J Immunol. 2013 Nov;43(11):2930-42. doi: 10.1002/eji.201343349. Epub 2013 Aug 25.

ABSTRACT

Tumor growth coincides with an accumulation of myeloid-derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic...

Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages

22/06/2012

Cancer Res. 2012 Aug 15;72(16):4165-77. doi: 10.1158/0008-5472.CAN-11-2994. Epub 2012 Jun 19.

ABSTRACT

Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in...

Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions

14/12/2011

Int J Dev Biol. 2011;55(7-9):861-7. doi: 10.1387/ijdb.113371dl.

ABSTRACT

Macrophages display remarkable plasticity, allowing these cells to adapt to changing microenvironments and perform functions as diverse as tissue development and homeostasis, inflammation, pathogen clearance...

Mononuclear phagocyte heterogeneity in cancer: different subsets and activation states reaching out at the tumor site

02/08/2011

Immunobiology. 2011 Nov;216(11):1192-202. doi: 10.1016/j.imbio.2011.06.007. Epub 2011 Jun 30.

ABSTRACT

Mononuclear phagocytes are amongst the most versatile cells of the body, contributing to tissue genesis and homeostasis and safeguarding the balance between pro- and anti-...

Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes

24/06/2010

Cancer Res. 2010 Jul 15;70(14):5728-39. doi: 10.1158/0008-5472.CAN-09-4672. Epub 2010 Jun 22.

ABSTRACT

Tumor-associated macrophages (TAM) form a major component of the tumor stroma. However, important concepts such as TAM heterogeneity and the nature of the monocytic TAM...

A method for the isolation and purification of mouse peripheral blood monocytes

12/05/2010

J Immunol Methods. 2010 Jul 31;359(1-2):1-10. doi: 10.1016/j.jim.2010.04.004. Epub 2010 May 8.

ABSTRACT

Studies in mice have advanced our understanding of the contribution of monocytes to inflammation and immunity. However, the lack of a straightforward and reliable method for...

Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes

04/09/2009

Blood. 2009 Nov 19;114(21):4664-74. doi: 10.1182/blood-2009-05-221598. Epub 2009 Sep 2.

ABSTRACT

Alternatively activated macrophages (AAMs), triggered by interleukin-4 (IL-4) and IL-13, play a modulating role during Th2 cytokine-driven pathologies, but their molecular armament...

IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection

07/01/2009

J Immunol. 2009 Jan 15;182(2):1107-18. doi: 10.4049/jimmunol.182.2.1107.

ABSTRACT

Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells...

Macrophages, PPARs, and Cancer

11/07/2008

PPAR Res. 2008;2008:169414. doi: 10.1155/2008/169414.

ABSTRACT

Mononuclear phagocytes often function as control switches of the immune system, securing the balance between pro- and anti-inflammatory reactions. For this purpose and depending on the activating stimuli, these cells...

Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity

15/02/2008

Blood. 2008 Apr 15;111(8):4233-44. doi: 10.1182/blood-2007-07-099226. Epub 2008 Feb 13.

ABSTRACT

The induction of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) is an important immune-evading mechanism used by tumors. However, the exact nature and function of MDSCs...

Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion

22/08/2006

Immunobiology. 2006;211(6-8):487-501. doi: 10.1016/j.imbio.2006.06.002. Epub 2006 Jul 21.

ABSTRACT

Mononuclear phagocytes often function as control switches of the immune system, securing the balance between pro- and anti-inflammatory reactions. For this purpose and depending on...