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2017
Saliba Hanadi, Heurtault Béatrice, Bouharoun-Tayoun Hasnaa, Flacher Vincent, Frisch Benoît, Fournel Sylvie, Chamat Soulaima
Enhancing tumor specific immune responses by transcutaneous vaccination Journal Article
In: Expert Review of Vaccines, vol. 16, no. 11, pp. 1079–1094, 2017, ISSN: 1744-8395.
Abstract | Links | BibTeX | Tags: Administration, Cancer vaccine, Cancer Vaccines, Clinical Trials as Topic, Cutaneous, Dendritic Cells, Humans, liposome, Liposomes, nanoparticle, Nanoparticles, Neoplasms, Skin, skin dendritic cell, Team-Mueller, transcutaneous vaccination, Treatment Outcome, Vaccination
@article{saliba_enhancing_2017,
title = {Enhancing tumor specific immune responses by transcutaneous vaccination},
author = {Hanadi Saliba and Béatrice Heurtault and Hasnaa Bouharoun-Tayoun and Vincent Flacher and Benoît Frisch and Sylvie Fournel and Soulaima Chamat},
doi = {10.1080/14760584.2017.1382357},
issn = {1744-8395},
year = {2017},
date = {2017-01-01},
journal = {Expert Review of Vaccines},
volume = {16},
number = {11},
pages = {1079--1094},
abstract = {INTRODUCTION: Our understanding of the involvement of the immune system in cancer control has increased over recent years. However, the development of cancer vaccines intended to reverse tumor-induced immune tolerance remains slow as most current vaccine candidates exhibit limited clinical efficacy. The skin is particularly rich with multiple subsets of dendritic cells (DCs) that are involved to varying degrees in the induction of robust immune responses. Transcutaneous administration of cancer vaccines may therefore harness the immune potential of these DCs, however, this approach is hampered by the impermeability of the stratum corneum. Innovative vaccine formulations including various nanoparticles, such as liposomes, are therefore needed to properly deliver cancer vaccine components to skin DCs. Areas covered: The recent insights into skin DC subsets and their functional specialization, the potential of nanoparticle-based vaccines in transcutaneous cancer vaccination and, finally, the most relevant clinical trial advances in liposomal and in cutaneous cancer vaccines will be discussed. Expert commentary: To define the optimal conditions for mounting protective skin DC-induced anti-tumor immune responses, investigation of the cellular and molecular interplay that controls tumor progression should be pursued in parallel with clinical development. The resulting knowledge will then be translated into improved cancer vaccines that better target the most appropriate immune players.},
keywords = {Administration, Cancer vaccine, Cancer Vaccines, Clinical Trials as Topic, Cutaneous, Dendritic Cells, Humans, liposome, Liposomes, nanoparticle, Nanoparticles, Neoplasms, Skin, skin dendritic cell, Team-Mueller, transcutaneous vaccination, Treatment Outcome, Vaccination},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Our understanding of the involvement of the immune system in cancer control has increased over recent years. However, the development of cancer vaccines intended to reverse tumor-induced immune tolerance remains slow as most current vaccine candidates exhibit limited clinical efficacy. The skin is particularly rich with multiple subsets of dendritic cells (DCs) that are involved to varying degrees in the induction of robust immune responses. Transcutaneous administration of cancer vaccines may therefore harness the immune potential of these DCs, however, this approach is hampered by the impermeability of the stratum corneum. Innovative vaccine formulations including various nanoparticles, such as liposomes, are therefore needed to properly deliver cancer vaccine components to skin DCs. Areas covered: The recent insights into skin DC subsets and their functional specialization, the potential of nanoparticle-based vaccines in transcutaneous cancer vaccination and, finally, the most relevant clinical trial advances in liposomal and in cutaneous cancer vaccines will be discussed. Expert commentary: To define the optimal conditions for mounting protective skin DC-induced anti-tumor immune responses, investigation of the cellular and molecular interplay that controls tumor progression should be pursued in parallel with clinical development. The resulting knowledge will then be translated into improved cancer vaccines that better target the most appropriate immune players.
2008
Muller Sylviane, Monneaux Fanny, Schall Nicolas, Rashkov Rasho K, Oparanov Boycho A, Wiesel Philippe, Geiger Jean-Marie, Zimmer Robert
Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial Journal Article
In: Arthritis and Rheumatism, vol. 58, no. 12, pp. 3873–3883, 2008, ISSN: 0004-3591.
Abstract | Links | BibTeX | Tags: Adolescent, Adult, Aged, Antibodies, Antinuclear, C-Reactive Protein, DNA, Female, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Male, Middle Aged, Monneaux, Peptide Fragments, Peptides, Severity of Illness Index, Spliceosomes, Systemic, Team-Dumortier, Treatment Outcome, Young Adult
@article{muller_spliceosomal_2008,
title = {Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial},
author = {Sylviane Muller and Fanny Monneaux and Nicolas Schall and Rasho K Rashkov and Boycho A Oparanov and Philippe Wiesel and Jean-Marie Geiger and Robert Zimmer},
doi = {10.1002/art.24027},
issn = {0004-3591},
year = {2008},
date = {2008-01-01},
journal = {Arthritis and Rheumatism},
volume = {58},
number = {12},
pages = {3873--3883},
abstract = {OBJECTIVE: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.},
keywords = {Adolescent, Adult, Aged, Antibodies, Antinuclear, C-Reactive Protein, DNA, Female, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Male, Middle Aged, Monneaux, Peptide Fragments, Peptides, Severity of Illness Index, Spliceosomes, Systemic, Team-Dumortier, Treatment Outcome, Young Adult},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.
