The fully synthetic glycopeptide MAG-Tn3 therapeutic vaccine induces tumor-specific cytotoxic antibodies in breast cancer patients

Autor: Cecile Artaud, Marie-Paule Sablin, Jacques Medioni, Pierre Rosenbaum, Sylvie Bay, Olivier Tredan, Christelle Ganneau, Suzette Delaloge, Delphine Loirat, Mario Campone, François Pein, Claude Leclerc, Andrea Varga, Carole Gourmelon
Přispěvatelé: Régulation Immunitaire et Vaccinologie, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], Chimie des Biomolécules - Chemistry of Biomolecules, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut Gustave Roussy (IGR), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Curie [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Léon Bérard [Lyon], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), The work was funded by the donors of the MAG-Tn3 program. GlaxoSmithKline Biological SA provided AS15 and preparing the final formulation of the MAG/AS15 vaccine., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Cancer Research
Antibodies
Neoplasm
Tn antigen
MESH: Adjuvants
Immunologic
Epitope
MESH: Cancer Vaccines
Jurkat Cells
0302 clinical medicine
Immunogenicity
Vaccine
Breast cancer
Cancer vaccine
MESH: Jurkat Cells
Immunology and Allergy
Medicine
MESH: Animals
MESH: Treatment Outcome
MESH: Aged
education.field_of_study
Vaccines
Synthetic
MESH: Middle Aged
biology
MESH: Antigens
Tumor-Associated
Carbohydrate
Vaccination
Glycopeptides
MESH: Immunogenicity
Vaccine
Middle Aged
QS21
MESH: Injections
Intramuscular
Glycopeptide
3. Good health
Treatment Outcome
Oncology
Female
Antibody
MESH: Neoplasm Recurrence
Local
Adult
MESH: Vaccines
Synthetic
Immunology
Population
Breast Neoplasms
Cancer Vaccines
Injections
Intramuscular
Antibodies
03 medical and health sciences
Immune system
Adjuvants
Immunologic
Animals
Humans
Antigens
Tumor-Associated
Carbohydrate
education
Aged
MESH: Glycopeptides
MESH: Humans
business.industry
MESH: Adult
MESH: Vaccination
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
MESH: Antibodies
Neoplasm
biology.protein
Neoplasm Recurrence
Local
business
MESH: Female
MESH: Breast Neoplasms
030215 immunology
Zdroj: Cancer Immunology, Immunotherapy
Cancer Immunology, Immunotherapy, Springer Verlag, 2020, 69 (5), pp.703-716. ⟨10.1007/s00262-020-02503-0⟩
Cancer Immunology, Immunotherapy, 2020, 69 (5), pp.703-716. ⟨10.1007/s00262-020-02503-0⟩
ISSN: 0340-7004
1432-0851
Popis: International audience; Cancer is one of the main causes of mortality worldwide and a major public health concern. Among various strategies, therapeutic vaccines have been developed to stimulate anti-tumoral immune responses. However, in spite of extensive studies, this approach suffers from a lack of efficacy. Recently, we designed the MAG-Tn3 vaccine, aiming to induce antibody responses against Tn, a tumor-associated carbohydrate antigen. The Tn antigen is of interest because it is expressed by several adenocarcinomas, but not normal cells. The fully synthetic glycopeptide vaccine MAG-Tn3 is composed of four arms built on three adjacent Tn moieties associated with the tetanus toxin-derived peptide TT830-844 CD4+ T-cell epitope. This promiscuous CD4+ T-cell epitope can bind to a wide range of HLA-DRB molecules and is thus expected to activate CD4+ T-cell responses in a large part of the human population. The MAG-Tn3 vaccine was formulated with the GSK-proprietary immunostimulant AS15, composed of CpG7909, MPL, and QS21, which has been shown to stimulate both innate and humoral responses, in addition to being well tolerated. Here, seven patients with localized breast cancer with a high-risk of relapse were immunized with the MAG-Tn3 vaccine formulated with AS15. The first results of phase I clinical trial demonstrated that all vaccinated patients developed high levels of Tn-specific antibodies. Moreover, these antibodies specifically recognized Tn-expressing human tumor cells and killed them through a complement-dependent cytotoxicity mechanism. Overall, this study establishes, for the first time, the capacity of a fully synthetic glycopeptide cancer vaccine to induce specific immune responses in humans.
Databáze: OpenAIRE
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