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Article ; Online: STxB as an Antigen Delivery Tool for Mucosal Vaccination

Eric Tartour / Ludger Johannes

Toxins, Vol 14, Iss 202, p

2022 Volume 202

Abstract: Immunotherapy against cancer and infectious disease holds the promise of high efficacy with minor side effects. Mucosal vaccines to protect against tumors or infections disease agents that affect the upper airways or the lung are still lacking, however. ... ...

Abstract	Immunotherapy against cancer and infectious disease holds the promise of high efficacy with minor side effects. Mucosal vaccines to protect against tumors or infections disease agents that affect the upper airways or the lung are still lacking, however. One mucosal vaccine candidate is the B-subunit of Shiga toxin, STxB. In this review, we compare STxB to other immunotherapy vectors. STxB is a non-toxic protein that binds to a glycosylated lipid, termed globotriaosylceramide (Gb3), which is preferentially expressed by dendritic cells. We review the use of STxB for the cross-presentation of tumor or viral antigens in a MHC class I-restricted manner to induce humoral immunity against these antigens in addition to polyfunctional and persistent CD4 + and CD8 + T lymphocytes capable of protecting against viral infection or tumor growth. Other literature will be summarized that documents a powerful induction of mucosal IgA and resident memory CD8 + T cells against mucosal tumors specifically when STxB-antigen conjugates are administered via the nasal route. It will also be pointed out how STxB-based vaccines have been shown in preclinical cancer models to synergize with other therapeutic modalities (immune checkpoint inhibitors, anti-angiogenic therapy, radiotherapy). Finally, we will discuss how molecular aspects such as low immunogenicity, cross-species conservation of Gb3 expression, and lack of toxicity contribute to the competitive positioning of STxB among the different DC targeting approaches. STxB thereby appears as an original and innovative tool for the development of mucosal vaccines in infectious diseases and cancer.
Keywords	glycolipid-lectin ; GL-Lect ; endosomal escape ; cross-presentation ; tissue resident memory T cells ; TRM ; Medicine ; R
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Humoral Immune Response to SARS-CoV-2 Vaccination after a Booster Vaccine Dose in Two Kidney Transplant Recipients with Fabry Disease and Variable Secondary Immunosuppressive Regimens

Lavinia Bernea / Oana R. Ailioaie / Nadine Benhamouda / Eric Tartour / Dominique P. Germain

Vaccines, Vol 9, Iss 1412, p

2021 Volume 1412

Abstract: The urgent need to fight the COVID-19 pandemic has accelerated the development of vaccines against SARS-CoV-2 and approval processes. Initial analysis of two-dose regimens with mRNA vaccines reported up to 95% efficacy against the original strain of the ... ...

Abstract	The urgent need to fight the COVID-19 pandemic has accelerated the development of vaccines against SARS-CoV-2 and approval processes. Initial analysis of two-dose regimens with mRNA vaccines reported up to 95% efficacy against the original strain of the SARS-CoV-2 virus. Challenges arose with the appearance of new strains of the virus, and reports that solid organ transplant recipients may have reduced vaccination success rates after a two-dose mRNA vaccination regimen encouraged health authorities to recommend a booster in immunocompromised patients. Fabry disease is an X-linked inherited lysosomal disorder, which may lead to chronic end-stage renal disease. We report on two patients with advanced Fabry disease, renal graft and adjunctive immunosuppressive therapies who exhibited variable humoral vaccination-related immune responses against SARS-CoV-2 after three vaccine doses. The first patient developed mild COVID-19 infection, while the second patient did not seroconvert after three shots of an mRNA vaccine. Both cases emphasize that patients with Fabry disease and renal graft are susceptible to develop a weak response to COVID-19 vaccination and highlight the importance of maintaining barrier protection measures. Vaccination of family members should be encouraged to lower the risk of viral transmission to immunocompromised, transplanted patients, including vaccinated ones.
Keywords	COVID-19 ; vaccine ; Fabry disease ; renal transplant ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Synthetic Melanin Acts as Efficient Peptide Carrier in Cancer Vaccine Strategy

Stefania Cuzzubbo / Benoit Roch / Guillaume Darrasse-Jèze / Benoit Hosten / Manon Leclercq / Nicolas Vignal / Claire Banissi / Eric Tartour / Antoine F. Carpentier

International Journal of Molecular Sciences, Vol 23, Iss 14975, p

2022 Volume 14975

Abstract: We previously reported that a novel peptide vaccine platform, based on synthetic melanin nanoaggregates, triggers strong cytotoxic immune responses and significantly suppresses tumor growth in mice. However, the mechanisms underlying such an efficacy ... ...

Abstract	We previously reported that a novel peptide vaccine platform, based on synthetic melanin nanoaggregates, triggers strong cytotoxic immune responses and significantly suppresses tumor growth in mice. However, the mechanisms underlying such an efficacy remained poorly described. Herein, we investigated the role of dendritic cells (DCs) in presenting the antigen embedded in the vaccine formulation, as well as the potential stimulatory effect of melanin upon these cells, in vitro by coculture experiments and ELISA/flow cytometry analysis. The vaccine efficiency was evaluated in FLT3-L −/− mice constitutively deficient in DC1, DC2, and pDCs, in Zbtb46 DTR chimera mice deficient in DC1 and DC2, and in Langerin DTR mice deficient in dermal DC1 and Langerhans cells. We concluded that DCs, and especially migratory conventional type 1 dendritic cells, seem crucial for mounting the immune response after melanin-based vaccination. We also assessed the protective effect of L-DOPA melanin on peptides from enzymatic digestion, as well as the biodistribution of melanin–peptide nanoaggregates, after subcutaneous injection using [ 18 F]MEL050 PET imaging in mice. L-DOPA melanin proved to act as an efficient carrier for peptides by fully protecting them from enzymatic degradation. L-DOPA melanin did not display any direct stimulatory effects on dendritic cells in vitro. Using PET imaging, we detected melanin–peptide nanoaggregates up to three weeks after subcutaneous injections within the secondary lymphoid tissues, which could explain the sustained immune response observed (up to 4 months) with this vaccine technology.
Keywords	melanin ; L-DOPA ; cancer vaccine ; adjuvant ; nanoparticles ; carrier ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Control of the adaptive immune response by tumor vasculature

LaetitiaMauge / EricTartour

Frontiers in Oncology, Vol

2014 Volume 4

Abstract: The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial ... ...

Abstract	The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by abnormal vessel structure and permeability, and by specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intratumoral immune responses and contribute to the development of intratumoral immunosuppression, which is a major mechanism for promoting the development, progression and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of antitumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.
Keywords	Adaptive Immunity ; tumor ; endothelial cell ; Immunological Synapse ; lymphocyte infiltration ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	570
Language	English
Publishing date	2014-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Analytical validation of an alternative method to quantify specific antibodies in 3 applications

Senant, Marie / Eric Tartour / Marie-Agnès Dragon-Durey / Pauline Bordereau

Journal of immunological methods. 2019 Jan., v. 464

2019

Abstract: The detection and the quantification of specific antibodies represent essential tools for the diagnosis and for the biological monitoring of immune humoral response in many clinical situations in particular in autoimmune diseases or in the context of ... ...

Abstract	The detection and the quantification of specific antibodies represent essential tools for the diagnosis and for the biological monitoring of immune humoral response in many clinical situations in particular in autoimmune diseases or in the context of immunotherapy using monoclonal antibodies.This article focuses on the development of a specific antibody measuring method (Patent n°PCT/IB2014/064437). The principle of this method is based on the combined use of a monoclonal antibody as standard and the protein G as immunoglobulins detecting agent.We performed a complete analytical validation of this method for the quantification of antibodies in three different applications: autoantibodies, alloantibodies and therapeutic monoclonal antibody. The results showed good performances compatible with the use of these assays as diagnostic tools.This method allows avoiding the use of products from human origin as reagent that causes ethical and infectious concerns but also storage and long term stock management problems. Moreover, this approach is particularly useful when no commercial reagent is available, especially in the case of rare diseases.
Keywords	autoantibodies ; autoimmune diseases ; environmental monitoring ; ethics ; immunoglobulins ; immunotherapy ; monoclonal antibodies
Language	English
Dates of publication	2019-01
Size	p. 40-46.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2018.10.008
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Control of the immune response by proangiogenic factors

MagaliTERME / SimonPERNOT / EricTARTOUR

Frontiers in Oncology, Vol

2014 Volume 4

Abstract: The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction is found. Thus, tumors develop mechanisms to ... ...

Abstract	The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction is found. Thus, tumors develop mechanisms to become invisible to the immune system, such as the induction of immunosuppressive cells which are able to inhibit the development of an efficient immune response. Molecules produced in the tumor microenvironment are involved in the occurrence of an immunosuppressive microenvironment. Recently, it has been shown that Vascular Endothelial Growth Factor -A (VEGF-A) exhibits immunosuppressive properties in addition to its proangiogenic activities. VEGF-A can induce the accumulation of immature dendritic cells, myeloid derived suppressor cells, regulatory T cells and inhibit the migration of T lymphocytes to the tumor. Other proangiogenic factors such as Placental Growth Factor (PlGF) could also participate in tumor-induced immunosuppression, but only few works have been performed on this point. Here, we review the impact of proangiogenic factors (especially VEGF-A) on immune cells. Anti-angiogenic molecules, which target VEGF-A/VEGFR axis, have been developed in the last decades and are commonly used to treat cancer patients. These drugs have anti-angiogenic properties but can also counteract the tumor-induced immunosuppression. Based on these immunomodulatory properties, anti-angiogenic molecules could be efficiently associated with immunotherapeutic strategies in preclinical models. These combinations are currently under investigation in cancer patients.
Keywords	Immunosuppression ; Immunotherapy ; tumor ; regulatory T cells ; MDSC ; proangiogenic factors ; VEGF-A ; PlGF ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2014-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors

Soumaya Karaki / Marie Anson / Thi Tran / Delphine Giusti / Charlotte Blanc / Stephane Oudard / Eric Tartour

Vaccines, Vol 4, Iss 4, p

2016 Volume 37

Abstract: Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%–80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T ... ...

Abstract	Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%–80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86). Enhanced T cell infiltration of various tumors has been demonstrated following this combination therapy. The timing of this combination appears to be critical to the success of this therapy and multiple combinations of immunomodulating antibodies (CPI antagonists or costimulatory pathway agonists) have reinforced the synergy with cancer vaccines. Only limited results are available in humans and this combined approach has yet to be validated. Comprehensive monitoring of the regulation of CPI and costimulatory molecules after administration of immunomodulatory antibodies (anti-PD1/PD-L1, anti-CTLA-4, anti-OX40, etc.) and cancer vaccines should help to guide the selection of the best combination and timing of this therapy.
Keywords	cancer vaccine ; checkpoint inhibitors ; immunotherapy ; combination therapy ; PD-1 ; PD-L1 ; CTLA-4 ; CD40 ; OX40 ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2016-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interstitial Lung Disease-Complicated Anti-MDA5 Antibody in Clinically Amyopathic Dermatomyositis Patients

Laurence Pacot / Jacques Pouchot / Nicolas De Prost / Marie Senant / Eric Tartour / Françoise Le Pimpec-Barthes / Dominique Israel-Biet / Marie-Agnes Dragon-Durey

Frontiers in Medicine, Vol

Report of Two Cases With Distinct Clinical Features

2020 Volume 7

Abstract: Two patients presented simultaneously to our hospital with distinct clinical features associated with the presence of anti-MDA5 antibodies: the first one was admitted for a skin rash resembling to a toxic epidermal necrosis (Lyell syndrome) and the ... ...

Abstract	Two patients presented simultaneously to our hospital with distinct clinical features associated with the presence of anti-MDA5 antibodies: the first one was admitted for a skin rash resembling to a toxic epidermal necrosis (Lyell syndrome) and the second one presented with pulmonary manifestations attributed to a diffuse fibrosing interstitial pneumonitis on chest CT-scan. In addition to the skin lesions involving 40% of the body surface area, the first patient developed a rapid diffuse interstitial pneumonitis with respiratory distress justifying the initiation of a systemic immunosuppressive treatment. However, she died 3 weeks after her admission from mesenteric thrombosis associated with septic shock. The second patient respiratory condition worsened despite an intensive immunosuppressive treatment with high doses of intravenous methylprednisolone and cyclophosphamide and plasmapheresis, and required lung transplantation. Anti-MDA5 antibody titer declined and disappeared on anti-rejection treatment. These two cases underline the diagnostic conundrum and the therapeutic difficulties in patients with anti-MDA5 antibodies and clinically amyopathic dermatomyositis (CADM) or interstitial lung disease (ILD), who may undergo rapidly-progressive and fatal outcome. Presence of anti-MDA5 antibodies should always be suspected when confronted to CADM patients with cutaneous ulcerations or ILD to allow a rapid and adapted treatment initiation.
Keywords	autoantibodies ; dermatomyositis ; skin rash ; interstitial lung disease ; anti-rejection therapy ; lung transplantation ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Decrease of Pro-Angiogenic Monocytes Predicts Clinical Response to Anti-Angiogenic Treatment in Patients with Metastatic Renal Cell Carcinoma

Cells, Vol 11, Iss 17, p

2022 Volume 17

Abstract: The modulation of subpopulations of pro-angiogenic monocytes (VEGFR-1 + CD14 and Tie2 + CD14) was analyzed in an ancillary study from the prospective PazopanIb versus Sunitinib patient preferenCE Study (PISCES) (NCT01064310), where metastatic renal cell ... ...

Abstract	The modulation of subpopulations of pro-angiogenic monocytes (VEGFR-1 + CD14 and Tie2 + CD14) was analyzed in an ancillary study from the prospective PazopanIb versus Sunitinib patient preferenCE Study (PISCES) (NCT01064310), where metastatic renal cell carcinoma (mRCC) patients were treated with two anti-angiogenic drugs, either sunitinib or pazopanib. Blood samples from 86 patients were collected prospectively at baseline (T1), and at 10 weeks (T2) and 20 weeks (T3) after starting anti-angiogenic therapy. Various subpopulations of myeloid cells (monocytes, VEGFR-1 + CD14 and Tie2 + CD14 cells) decreased during treatment. When patients were divided into two subgroups with a decrease (defined as a >20% reduction from baseline value) (group 1) or not (group 2) at T3 for VEGFR-1 + CD14 cells, group 1 patients presented a median PFS and OS of 24 months and 37 months, respectively, compared with a median PFS of 9 months ( p = 0.032) and a median OS of 16 months ( p = 0.033) in group 2 patients. The reduction in Tie2 + CD14 at T3 predicted a benefit in OS at 18 months after therapy ( p = 0.04). In conclusion, in this prospective clinical trial, a significant decrease in subpopulations of pro-angiogenic monocytes was associated with clinical response to anti-angiogenic drugs in patients with mRCC.
Keywords	angiogenesis ; myeloid cells ; biomarker ; pro-angiogenic monocytes ; renal cell carcinoma ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Synthetic melanin bound to subunit vaccine antigens significantly enhances CD8+ T-cell responses.

Antoine F Carpentier / Frédéric Geinguenaud / Thi Tran / Floraly Sejalon / Antoine Martin / Laurence Motte / Eric Tartour / Claire Banissi

PLoS ONE, Vol 12, Iss 7, p e

2017 Volume 0181403

Abstract: Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be ... ...

Abstract	Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides. Immunization with melanin-bound peptides efficiently triggered CTL responses in mice, even against self-antigens and at a very low dose of peptides (microgram range). Immunization against a tumor antigen inhibited the growth of established tumors in mice, an effect that was abrogated by the depletion of CD8+ lymphocytes. These results demonstrate the efficacy of melanin as a vaccine adjuvant.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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