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Article: Azoximer bromide and hydroxyapatite: promising immune adjuvants in cancer.

Rossi, Jean-François / Frayssinet, Patrick / Matciyak, Maksim / Tupitsyn, Nikolai

2024 Volume 20, Issue 12

Abstract: Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations. There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers. Immune adjuvant mechanisms of ... ...

Abstract	Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations. There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers. Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response, followed by the adaptive immune response. The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells. Most immune adjuvants are associated with a vaccine or incorporated into the new generation of mRNA vaccines. Few immune adjuvants are used as drugs. Hydroxyapatite (HA) ceramics and azoximer bromide (AZB) are overlooked molecules that were used in early clinical trials, which demonstrated clinical efficacy and excellent tolerance profiles. HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas. AZB, an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia, the Commonwealth of Independent States, and Slovakia for infectious and inflammatory diseases, is and now being developed for use in cancer with promising results. These two immune adjuvants can be combined in various immunotherapy strategies.
MeSH term(s)	Animals ; Dogs ; Humans ; Adjuvants, Immunologic/pharmacology ; Adjuvants, Immunologic/therapeutic use ; Vaccines ; Neoplasms/drug therapy ; Hydroxyapatites ; Piperazines ; Polymers
Chemical Substances	azoximer bromide (90G53638ZD) ; Adjuvants, Immunologic ; Vaccines ; Hydroxyapatites ; Piperazines ; Polymers
Language	English
Publishing date	2024-01-03
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2676322-9
ISSN	2095-3941
ISSN	2095-3941
DOI	10.20892/j.issn.2095-3941.2023.0222
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Article ; Online: Tocilizumab in Treatment for Patients With COVID-19.

Rossi, Jean-François / Chiang, Hao-Chun / Klein, Bernard

JAMA internal medicine

2021 Volume 181, Issue 7, Page(s) 1018–1019

MeSH term(s)	Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy ; Humans ; SARS-CoV-2
Chemical Substances	Antibodies, Monoclonal, Humanized ; tocilizumab (I031V2H011)
Language	English
Publishing date	2021-04-05
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2699338-7
ISSN	2168-6114 ; 2168-6106
ISSN (online)	2168-6114
ISSN	2168-6106
DOI	10.1001/jamainternmed.2021.0395
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Article ; Online: Targeted Therapies in Adult B-Cell Malignancies.

Rossi, Jean-François

BioMed research international

2015 Volume 2015, Page(s) 217593

Abstract: B-lymphocytes are programmed for the production of immunoglobulin (Ig) after antigen presentation, in the context of T-lymphocyte control within lymphoid organs. During this differentiation/activation process, B-lymphocytes exhibit different restricted ... ...

Abstract	B-lymphocytes are programmed for the production of immunoglobulin (Ig) after antigen presentation, in the context of T-lymphocyte control within lymphoid organs. During this differentiation/activation process, B-lymphocytes exhibit different restricted or common surface markers, activation of cellular pathways that regulate cell cycle, metabolism, proteasome activity, and protein synthesis. All molecules involved in these different cellular mechanisms are potent therapeutic targets. Nowadays, due to the progress of the biology, more and more targeted drugs are identified, a situation that is correlated with an extended field of the targeted therapy. The full knowledge of the cellular machinery and cell-cell communication allows making the best choice to treat patients, in the context of personalized medicine. Also, focus should not be restricted to the immediate effects observed as clinical endpoints, that is, response rate, survival markers with conventional statistical methods, but it should consider the prediction of different clinical consequences due to other collateral drug targets, based on new methodologies. This means that new reflection and new bioclinical follow-up have to be monitored, particularly with the new drugs used with success in B-cell malignancies. This review discussed the principal aspects of such evident bioclinical progress.
MeSH term(s)	B-Lymphocytes/pathology ; Biomarkers/metabolism ; Cell Membrane/metabolism ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Tumor Microenvironment
Chemical Substances	Biomarkers
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2015/217593
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Article ; Online: Dynamic Immune/Inflammation Precision Medicine

Jean-François Rossi / Zhao Yang Lu / Cesare Massart / Kalle Levon

Frontiers in Immunology, Vol

The Good and the Bad Inflammation in Infection and Cancer

2021 Volume 12

Abstract: Normal or “good” inflammation process starts from a local cellular response against injury or any infectious agent, with the activation of neutrophils, macrophages, Langerhans cells, dendritic cells, and innate immune cells. Cytokines and chemokines are ... ...

Abstract	Normal or “good” inflammation process starts from a local cellular response against injury or any infectious agent, with the activation of neutrophils, macrophages, Langerhans cells, dendritic cells, and innate immune cells. Cytokines and chemokines are produced to amplify the local inflammatory process followed by the migration of immune cells to the regional lymph nodes where adaptive immune response is initiated. Systemic inflammation enhances the biological response to mobilize additional cells from central and peripheral immune/hematopoietic system. Local mechanisms to limit inflammation are initiated and lead to healing. During the normal inflammatory process, there is a balance between the production of inflammatory chemokines/cytokines such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6 and IL-1 and the production of compounds that limit inflammation and have an immune suppressive effect, such as IL-10 and Transforming Factor (TGF) β. IL-6 and IL-6/soluble IL-6 Receptor (R) complex stimulate liver cells to produce inflammatory proteins, which represents the systemic inflammation response. The magnitude and the duration of the systemic inflammatory response are linked to the cause, under genetic and epigenetic control. Significant inflammation as seen in septic shock, in severe forms of infections or in certain active cancers, represents the “bad inflammation”, correlated with a poor prognosis. In addition, the persistence of a chronic smoldering inflammation may lead to pathological situations which are observed in the majority of inflammatory, degenerative, dysmetabolic, or dysimmune diseases and cancer. Chronic smoldering inflammation is a cross between different pathological situations possibly linked. In addition, within the tumor microenvironment, inflammatory process results from different cellular mechanisms modulated by metabolic and vascular changes. On the contrary, a limited and balanced inflammation initiates the normal immune response, including the adaptive response which amplifies ...
Keywords	inflammation ; infection ; cancer ; precision medicine ; immune therapy ; Immunologic diseases. Allergy ; RC581-607
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeted Therapies in Adult B-Cell Malignancies

Jean-François Rossi

BioMed Research International, Vol

2015 Volume 2015

Abstract	B-lymphocytes are programmed for the production of immunoglobulin (Ig) after antigen presentation, in the context of T-lymphocyte control within lymphoid organs. During this differentiation/activation process, B-lymphocytes exhibit different restricted or common surface markers, activation of cellular pathways that regulate cell cycle, metabolism, proteasome activity, and protein synthesis. All molecules involved in these different cellular mechanisms are potent therapeutic targets. Nowadays, due to the progress of the biology, more and more targeted drugs are identified, a situation that is correlated with an extended field of the targeted therapy. The full knowledge of the cellular machinery and cell-cell communication allows making the best choice to treat patients, in the context of personalized medicine. Also, focus should not be restricted to the immediate effects observed as clinical endpoints, that is, response rate, survival markers with conventional statistical methods, but it should consider the prediction of different clinical consequences due to other collateral drug targets, based on new methodologies. This means that new reflection and new bioclinical follow-up have to be monitored, particularly with the new drugs used with success in B-cell malignancies. This review discussed the principal aspects of such evident bioclinical progress.
Keywords	Medicine ; R
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dynamic Immune/Inflammation Precision Medicine: The Good and the Bad Inflammation in Infection and Cancer.

Rossi, Jean-François / Lu, Zhao Yang / Massart, Cesare / Levon, Kalle

Frontiers in immunology

2021 Volume 12, Page(s) 595722

Abstract: Normal or "good" inflammation process starts from a local cellular response against injury or any infectious agent, with the activation of neutrophils, macrophages, Langerhans cells, dendritic cells, and innate immune cells. Cytokines and chemokines are ... ...

Abstract	Normal or "good" inflammation process starts from a local cellular response against injury or any infectious agent, with the activation of neutrophils, macrophages, Langerhans cells, dendritic cells, and innate immune cells. Cytokines and chemokines are produced to amplify the local inflammatory process followed by the migration of immune cells to the regional lymph nodes where adaptive immune response is initiated. Systemic inflammation enhances the biological response to mobilize additional cells from central and peripheral immune/hematopoietic system. Local mechanisms to limit inflammation are initiated and lead to healing. During the normal inflammatory process, there is a balance between the production of inflammatory chemokines/cytokines such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6 and IL-1 and the production of compounds that limit inflammation and have an immune suppressive effect, such as IL-10 and Transforming Factor (TGF) β. IL-6 and IL-6/soluble IL-6 Receptor (R) complex stimulate liver cells to produce inflammatory proteins, which represents the systemic inflammation response. The magnitude and the duration of the systemic inflammatory response are linked to the cause, under genetic and epigenetic control. Significant inflammation as seen in septic shock, in severe forms of infections or in certain active cancers, represents the "bad inflammation", correlated with a poor prognosis. In addition, the persistence of a chronic smoldering inflammation may lead to pathological situations which are observed in the majority of inflammatory, degenerative, dysmetabolic, or dysimmune diseases and cancer. Chronic smoldering inflammation is a cross between different pathological situations possibly linked. In addition, within the tumor microenvironment, inflammatory process results from different cellular mechanisms modulated by metabolic and vascular changes. On the contrary, a limited and balanced inflammation initiates the normal immune response, including the adaptive response which amplifies any immunotherapy, including vaccines. Immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells are associated with cytokine release syndrome, a clinical risk leading to the use of anti-cytokine drugs. Nowadays, it is time to monitor the dynamic inflammatory process for a better immune precision medicine in both infections and cancer.
MeSH term(s)	Animals ; Biomarkers ; Disease Management ; Disease Susceptibility/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Inflammation/diagnosis ; Inflammation/etiology ; Inflammation/therapy ; Inflammation Mediators ; Neoplasms/diagnosis ; Neoplasms/etiology ; Neoplasms/therapy ; Precision Medicine
Chemical Substances	Biomarkers ; Inflammation Mediators
Language	English
Publishing date	2021-02-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.595722
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Article: The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein.

Piacentini, Sara / Riccio, Anna / Santopolo, Silvia / Pauciullo, Silvia / La Frazia, Simone / Rossi, Antonio / Rossignol, Jean-Francois / Santoro, M Gabriella

Frontiers in microbiology

2023 Volume 14, Page(s) 1206951

Abstract: ... ...

Abstract	Coronaviridae
Language	English
Publishing date	2023-08-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1206951
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Article ; Online: Immune precision medicine for cancer: a novel insight based on the efficiency of immune effector cells.

Rossi, Jean-François / Céballos, Patrice / Lu, Zhao-Yang

Cancer communications (London, England)

2019 Volume 39, Issue 1, Page(s) 34

Abstract: Cancer cell growth is associated with immune surveillance failure. Nowadays, restoring the desired immune response against cancer cells remains a major therapeutic strategy. Due to the recent advances in biological knowledge, efficient therapeutic tools ... ...

Abstract	Cancer cell growth is associated with immune surveillance failure. Nowadays, restoring the desired immune response against cancer cells remains a major therapeutic strategy. Due to the recent advances in biological knowledge, efficient therapeutic tools have been developed to support the best bio-clinical approaches for immune precision therapy. One of the most important successes in immune therapy is represented by the applicational use of monoclonal antibodies, particularly the use of rituximab for B-cell lymphoproliferative disorders. More recently, other monoclonal antibodies have been developed, to inhibit immune checkpoints within the tumor microenvironment that limit immune suppression, or to enhance some immune functions with immune adjuvants through different targets such as Toll-receptor agonists. The aim is to inhibit cancer proliferation by the diminishing/elimination of cancer residual cells and clinically improving the response duration with no or few adverse effects. This effect is supported by enhancing the number, functions, and activity of the immune effector cells, including the natural killer (NK) lymphocytes, NKT-lymphocytes, γδ T-lymphocytes, cytotoxic T-lymphocytes, directly or indirectly through vaccines particularly with neoantigens, and by lowering the functions of the immune suppressive cells. Beyond these new therapeutics and their personalized usage, new considerations have to be taken into account, such as epigenetic regulation particularly from microbiota, evaluation of transversal functions, particularly cellular metabolism, and consideration to the clinical consequences at the body level. The aim of this review is to discuss some practical aspects of immune therapy, giving to clinicians the concept of immune effector cells balancing between control and tolerance. Immunological precision medicine is a combination of modern biological knowledge and clinical therapeutic decisions in a global vision of the patient.
MeSH term(s)	Cancer Vaccines ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Disease Susceptibility/immunology ; Humans ; Immunotherapy/methods ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Neoplasms/diagnosis ; Neoplasms/immunology ; Neoplasms/therapy ; Precision Medicine/methods ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Treatment Outcome
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2019-06-14
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2523-3548
ISSN (online)	2523-3548
DOI	10.1186/s40880-019-0379-3
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Article ; Online: Phase I study of atacicept in relapsed/refractory multiple myeloma (MM) and Waldenström's macroglobulinemia.

Rossi, Jean-François

Clinical lymphoma, myeloma & leukemia

2011 Volume 11, Issue 1, Page(s) 136–138

Abstract: Atacicept, a specific inhibitor of BLys and APRIL, was used in a phase I study for 14 patients with myeloma (MM) and 4 with Waldenström's macroglobulinemia (WM). They received 1 cycle of 5 once-weekly s.c. injections, followed by an extension if in ... ...

Abstract	Atacicept, a specific inhibitor of BLys and APRIL, was used in a phase I study for 14 patients with myeloma (MM) and 4 with Waldenström's macroglobulinemia (WM). They received 1 cycle of 5 once-weekly s.c. injections, followed by an extension if in stable disease or in response. The maximum tolerated dose was not identified. Of 11 patients with MM who completed initial treatment, 5 patients were progression-free after cycle 1 and 4 patients were progression-free after extended therapy. Of 4 patients with WM, 3 patients were progression-free after cycle 1. Polyclonal immunoglobulin isotypes and total B cells were reduced. Plasma concentrations of soluble CD 138 decreased. Biological effect was more pronounced in WM. Of the 16 patients tested at baseline, 13 had measurable levels of free APRIL (≥25 ng/mL). In this small series, no correlations were apparent between baseline levels of free APRIL and biological or clinical response criteria.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma/drug therapy ; Recombinant Fusion Proteins/administration & dosage ; Recombinant Fusion Proteins/adverse effects ; Recurrence ; Waldenstrom Macroglobulinemia/drug therapy
Chemical Substances	Recombinant Fusion Proteins ; TACI receptor-IgG Fc fragment fusion protein (K3D9A0ICQ3)
Language	English
Publishing date	2011-03-31
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	2540992-X
ISSN	2152-2669 ; 2152-2650
ISSN (online)	2152-2669
ISSN	2152-2650
DOI	10.3816/CLML.2011.n.031
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Article ; Online: Clinical and Serological Follow-Up of 216 Patients with Hematological Malignancies after Vaccination with Pfizer-BioNT162b2 mRNA COVID-19 in a Real-World Study

Jean-François Rossi / Emmanuel Bonnet / Christel Castelli / Marion Velensek / Emma Wisniewski / Sophie Heraud / Rania Boustany / Céleste David / Jérôme Dinet / Roland Sicard / Jean-Pierre Daures / Marion Bonifacy / Lysiane Mousset / Emmanuel Goffart

Vaccines, Vol 11, Iss 493, p

2023 Volume 493

Abstract: Hematological malignancies (HMs) have heterogeneous serological responses after vaccination due to disease or treatment. The aim of this real-world study was to analyze it after Pfizer-BioNT162b2 mRNA vaccination in 216 patients followed up for 1 year. ... ...

Abstract	Hematological malignancies (HMs) have heterogeneous serological responses after vaccination due to disease or treatment. The aim of this real-world study was to analyze it after Pfizer-BioNT162b2 mRNA vaccination in 216 patients followed up for 1 year. The first 43 patients had an initial follow-up by a telemedicine (TM) system with no major events reported. The anti-spike IgG antibodies were checked 3–4 weeks post-first vaccination and every 3–4 months, by two standard bioassays and a rapid serological test (RST). Vaccine boosts were given when the level was <7 BAU/mL. Patients who did not seroconvert after 3–4 doses received tixagevimab/cilgavimab (TC). Fifteen results were discordant between two standard bioassays. Good agreement was observed between the standard and RST in 97 samples. After two doses, 68% were seroconverted (median = 59 BAU/mL) with a median of 162 BAU/mL and 9 BAU/mL, respectively, in untreated and treated patients ( p < 0.001), particularly for patients receiving rituximab. Patients with gammaglobulin levels < 5 g/L had reduced seroconversion compared to higher levels ( p = 0.019). The median levels were 228 BAU/mL post-second dose if seroconverted post-first and second, or if seroconverted only post-second dose. A total of 68% of post-second dose negative patients were post-third dose positive. A total of 16% received TC, six with non-severe symptomatic COVID-19 within 15–40 days. Personalized serological follow-up should apply particularly to patients with HMs.
Keywords	COVID-19 ; serological follow-up ; hematological malignancies ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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