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2 results on '"MESH : Immunization, Passive"'

1. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up

Author

Gilles Salles, Philippe Colombat, Charles Foussard, Franck Morschhauser, F. Lazreg, Pierre Soubeyran, Corinne Haioun, Vincent Delwail, Nicole Brousse, Catherine Sebban, Pauline Brice, Philippe Solal-Celigny, Hervé Tilly, Catherine Thieblemont, Loïc Bergougnoux, Eric Deconinck, Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hématologie, Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel Dieu, Service d'Oncologie Médicale, Centre Léon Bérard [Lyon], Service d'oncologie, CRLCC Henri Becquerel, Service d'Hématologie, Roche, Onco-radiothérapie, hématologie, Centre Jean Bernard, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Bretonneau-CHRU Tours, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Angers-Hôtel Dieu, and Saas, Philippe

Subjects
Male, MESH : Immunization, Passive, MESH : Induction Chemotherapy, Follicular lymphoma, Kaplan-Meier Estimate, Gastroenterology, Antibodies, Monoclonal, Murine-Derived, MESH: Lymphoma, Follicular, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Lymphoma, Follicular, MESH: Treatment Outcome, education.field_of_study, MESH: Middle Aged, MESH : Neoplasm Recurrence, Local, Induction Chemotherapy, Hematology, MESH: Follow-Up Studies, MESH : Adult, Middle Aged, MESH: Induction Chemotherapy, 3. Good health, MESH : Antineoplastic Agents, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, MESH: Immunization, Passive, MESH: Neoplasm Recurrence, Local, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, Population, Antineoplastic Agents, MESH : Treatment Outcome, Disease-Free Survival, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH : Middle Aged, Progression-free survival, education, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, MESH : Lymphoma, Follicular, MESH : Humans, Immunization, Passive, Induction chemotherapy, MESH : Follow-Up Studies, MESH: Adult, medicine.disease, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Lymphoma, Surgery, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, Neoplasm Recurrence, Local, business, Diffuse large B-cell lymphoma, MESH: Female, Progressive disease, Follow-Up Studies, 030215 immunology
Abstract

International audience; BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.

Published
2012

2. Antibody-dependent cell cytotoxicity synapses form in mice during tumor-specific antibody immunotherapy

Author

André Nicolas, Otto Pritsch, Sophie Viel, Sebastian Amigorena, Pablo Oppezzo, Adele Heitzmann, Xavier Sastre-Garau, Pascale Hubert, Eduardo Osinaga, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Département de Biologie des Tumeurs, Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Departamento de inmunobiologia, Facultad de Medicina- Universidad de la República [Montevideo] (UCUR), This work was financially supported by the Institut National de la Sante et de la Recherche Medicale, the Association pour la Recherche sur le Cancer (ARC), the Institut Curie, the EC grant ENCITE, Health-F5-2008-201842, the Institut National du Cancer (INCa)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Institut Curie, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), INSTITUT CURIE, Réseau International des Instituts Pasteur ( RIIP ) -Institut Pasteur de Montevideo, and Universidad de la República-Facultad de Medicina

Subjects
Immunological Synapses, Antibodies, Neoplasm, medicine.medical_treatment, MESH : Breast Neoplasms, MESH: Neutrophils, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Antibodies, Monoclonal, MESH : Neutrophils, Mice, MESH : Antibody-Dependent Cell Cytotoxicity, 0302 clinical medicine, Antibody Specificity, MESH: Animals, MESH : Tumor Microenvironment, MESH : Receptors, IgG, MESH : Macrophages, Ovarian Neoplasms, 0303 health sciences, MESH: Antigens, Tumor-Associated, Carbohydrate, Antibodies, Monoclonal, MESH: Cystadenocarcinoma, Serous, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Monoclonal, MESH: Immunization, Passive, Antibody, MESH: Receptors, IgG, Monoclonal antibody, MESH : Antigens, Tumor-Associated, Carbohydrate, 03 medical and health sciences, Antigen, In vivo, Humans, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Antineoplastic Agents, Alkylating, Cyclophosphamide, MESH: Humans, Macrophages, MESH : Humans, Antibody-Dependent Cell Cytotoxicity, Immunization, Passive, MESH: Cyclophosphamide, Immunotherapy, Cystadenocarcinoma, Serous, MESH: Antibodies, Monoclonal, Humanized, MESH: Female, Cancer Research, MESH: Combined Modality Therapy, MESH : Immunization, Passive, Neutrophils, MESH: Antineoplastic Agents, Alkylating, MESH: Tumor Microenvironment, Tumor Microenvironment, MESH : Female, MESH : Cyclophosphamide, MESH : Immunological Synapses, MESH : Antibody Specificity, MESH : Cystadenocarcinoma, Serous, Antibody-dependent cell-mediated cytotoxicity, Mice, Inbred BALB C, biology, Combined Modality Therapy, MESH: Ovarian Neoplasms, MESH : Antibodies, Monoclonal, Female, MESH : Antibodies, Neoplasm, MESH : Mammary Neoplasms, Experimental, MESH: Cell Line, Tumor, medicine.drug_class, MESH : Antineoplastic Agents, Alkylating, MESH: Mammary Neoplasms, Experimental, MESH: Mice, Inbred BALB C, Breast Neoplasms, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, MESH : Antibodies, Monoclonal, Humanized, Cell Line, Tumor, MESH: Immunological Synapses, MESH : Mice, medicine, MESH: Antibody-Dependent Cell Cytotoxicity, Animals, Antigens, Tumor-Associated, Carbohydrate, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Antibody Specificity, MESH: Mice, MESH : Mice, Inbred BALB C, 030304 developmental biology, Innate immune system, MESH : Ovarian Neoplasms, MESH : Cell Line, Tumor, Receptors, IgG, Mammary Neoplasms, Experimental, MESH: Macrophages, Trastuzumab, Molecular biology, MESH: Antibodies, Neoplasm, biology.protein, MESH : Animals, MESH : Combined Modality Therapy, MESH: Breast Neoplasms
Abstract

Antibody-dependent cell cytotoxicity (ADCC) plays a critical role in monoclonal antibody (mAb)-mediated cancer therapy. ADCC, however, has not been directly shown in vivo but inferred from the requirement for IgG Fc receptors (FcγR) in tumor rejection in mice. Here, we investigated the mechanism of action of a Tn antigen-specific chimeric mAb (Chi-Tn), which binds selectively to a wide variety of carcinomas, but not to normal tissues, in both humans and mice. Chi-Tn mAb showed no direct toxicity against carcinomas cell lines in vitro but induced the rejection of a murine breast tumor in 80% to 100% of immunocompetent mice, when associated with cyclophosphamide. Tumor rejection was abolished in Fc receptors–associated γ chain (FcR-γ)–deficient mice, suggesting a role for ADCC. Indeed, tumor cells formed stable conjugates in vivo with FcR-γ chain-expressing macrophages and neutrophils in Chi-Tn mAb-treated but not in control mAb-treated mice. The contact zone between tumor cells and ADCC effectors accumulated actin, FcγR and phospho-tyrosines. The in vivo formed ADCC synapses were organized in multifocal supra-molecular activation clusters. These results show that in vivo ADCC mediated by macrophages and neutrophils during tumor rejection by Chi-Tn mAb involves a novel type of multifocal immune synapse between effectors of innate immunity and tumor cells. Cancer Res; 71(15); 5134–43. ©2011 AACR.

Published
2011

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