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[PMID]:27771496
[Au] Autor:Cabrero M; Martin A; Briones J; Gayoso J; Jarque I; López J; Grande C; Heras I; Arranz R; Bernal T; Perez-Lopez E; López-Godino O; Conde E; Caballero D
[Ad] Endereço:Hematology Department, Hospital Universitario Salamanca and IBSAL (Instituto Biosanitario de Salamanca), Spain.
[Ti] Título:Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.
[So] Source:Biol Blood Marrow Transplant;23(1):53-59, 2017 Jan.
[Is] ISSN:1523-6536
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m i.v. (days -3 and -2) plus melphalan 70 mg/m i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfoma de Células B/terapia
Terapia de Salvação/métodos
Condicionamento Pré-Transplante/métodos
[Mh] Termos MeSH secundário: Adulto
Feminino
Transplante de Células-Tronco Hematopoéticas/métodos
Transplante de Células-Tronco Hematopoéticas/mortalidade
Seres Humanos
Linfoma de Células B/mortalidade
Masculino
Melfalan/administração & dosagem
Meia-Idade
Radioimunoterapia/métodos
Radioimunoterapia/mortalidade
Terapia de Salvação/mortalidade
Análise de Sobrevida
Tiotepa/administração & dosagem
Condicionamento Pré-Transplante/mortalidade
Transplante Homólogo
Vidarabina/administração & dosagem
Vidarabina/análogos & derivados
Radioisótopos de Ítrio/uso terapêutico
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Yttrium Radioisotopes); 4Q52C550XK (ibritumomab tiuxetan); 905Z5W3GKH (Thiotepa); FA2DM6879K (Vidarabine); P2K93U8740 (fludarabine); Q41OR9510P (Melphalan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28466487
[Au] Autor:Epperla N; Pham AQ; Burnette BL; Wiseman GA; Habermann TM; Macon WR; Ansell SM; Inwards DJ; Micallef IN; Johnston PB; Markovic SN; Porrata LF; Colgan JP; Ristow KM; Nowakowski GS; Witzig TE
[Ad] Endereço:Department of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
[Ti] Título:Risk of histological transformation and therapy-related myelodysplasia/acute myeloid leukaemia in patients receiving radioimmunotherapy for follicular lymphoma.
[So] Source:Br J Haematol;178(3):427-433, 2017 08.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively (P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (tMDS/AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/AML in non-fludarabine treated patients (n = 90) versus fludarabine treated (n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT.
[Mh] Termos MeSH primário: Leucemia Mieloide Aguda/etiologia
Linfoma Folicular/terapia
Síndromes Mielodisplásicas/etiologia
Segunda Neoplasia Primária/etiologia
Radioimunoterapia/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anticorpos Monoclonais/efeitos adversos
Anticorpos Monoclonais/uso terapêutico
Quimioterapia Adjuvante/efeitos adversos
Bases de Dados Factuais
Feminino
Seres Humanos
Masculino
Meia-Idade
Neoplasias Induzidas por Radiação/etiologia
Radioimunoterapia/métodos
Fatores de Risco
Rituximab/efeitos adversos
Rituximab/uso terapêutico
Vidarabina/efeitos adversos
Vidarabina/análogos & derivados
Vidarabina/uso terapêutico
Adulto Jovem
Radioisótopos de Ítrio/efeitos adversos
Radioisótopos de Ítrio/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Yttrium Radioisotopes); 4F4X42SYQ6 (Rituximab); 4Q52C550XK (ibritumomab tiuxetan); FA2DM6879K (Vidarabine); P2K93U8740 (fludarabine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14688


  3 / 2973 MEDLINE  
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[PMID]:28940863
[Au] Autor:Kramer K; Pandit-Taskar N; Humm JL; Zanzonico PB; Haque S; Dunkel IJ; Wolden SL; Donzelli M; Goldman DA; Lewis JS; Lyashchenko SK; Khakoo Y; Carrasquillo JA; Souweidane MM; Greenfield JP; Lyden D; De Braganca KD; Gilheeney SW; Larson SM; Cheung NV
[Ad] Endereço:Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York.
[Ti] Título:A phase II study of radioimmunotherapy with intraventricular I-3F8 for medulloblastoma.
[So] Source:Pediatr Blood Cancer;65(1), 2018 Jan.
[Is] ISSN:1545-5017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular I-labeled 3F8 in patients with MB on a phase II clinical trial. METHODS: Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) I-3F8 or I-3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) I-3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region-of-interest analyses on serial imaging scans. Disease evaluation included pre- and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6-12 months thereafter. RESULTS: Forty-three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment-related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0-2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3-55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18-0.88, P = 0.024). CONCLUSIONS: cRIT with I-3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high-risk or recurrent MB.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Murinos/administração & dosagem
Antineoplásicos Imunológicos/administração & dosagem
Neoplasias Cerebelares/radioterapia
Radioisótopos do Iodo/administração & dosagem
Meduloblastoma/radioterapia
Radioimunoterapia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Neoplasias Cerebelares/líquido cefalorraquidiano
Neoplasias Cerebelares/diagnóstico por imagem
Neoplasias Cerebelares/mortalidade
Criança
Pré-Escolar
Intervalo Livre de Doença
Feminino
Seres Humanos
Lactente
Injeções Intraventriculares
Masculino
Meduloblastoma/líquido cefalorraquidiano
Meduloblastoma/diagnóstico por imagem
Meduloblastoma/mortalidade
Taxa de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Murine-Derived); 0 (Antineoplastic Agents, Immunological); 0 (Iodine Radioisotopes)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171129
[Lr] Data última revisão:
171129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170924
[St] Status:MEDLINE
[do] DOI:10.1002/pbc.26754


  4 / 2973 MEDLINE  
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[PMID]:29069013
[Au] Autor:Mi YX; Sui X; Huang JM; Wei LG; Xie P
[Ad] Endereço:aDepartment of Nuclear Medicine, Shanxi Provincial Cancer Hospital, Taiyuan City bDepartment of Ultrasound cDepartment of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
[Ti] Título:Incidentally polycystic kidney disease identified by SPECT/CT with post-therapy radioiodine scintigraphy in a patient with differentiated thyroid carcinoma: A case report.
[So] Source:Medicine (Baltimore);96(43):e8348, 2017 Oct.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Post-therapy or diagnostic whole-body radioiodine scintigraphy is widely employed to evaluate the residual, recurrence, or metastases of differentiated thyroid carcinoma because of the high sensitivity and accuracy. However, it has pitfalls. PATIENT CONCERNS: We described a 63-year-old male with a history of papillary thyroid carcinoma who was referred for iodine-131 ablation therapy. The post-therapy iodine-131 whole-body images demonstrated abnormal increased uptake of the tracer in the regions of bilateral upper abdomen. DIAGNOSES: The single photon emission computed tomography/computed tomography (SPECT/CT) showed the abnormal Iactivity was corresponded to multiple irregular cystic low densities in the both kidneys on the low-dose computed tomography images, so the diagnosis of polycystic kidney disease was confirmed. INTERVENTIONS AND OUTCOMES: The patient responded well to the lifestyle-based treatments. LESSONS: Polycystic kidney disease was one of the etiologies of the false-positive findings in the radioiodine scintigraphy.
[Mh] Termos MeSH primário: Carcinoma Papilar
Doenças Renais Policísticas/diagnóstico
Radioimunoterapia/métodos
Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos
Neoplasias da Glândula Tireoide
[Mh] Termos MeSH secundário: Carcinoma Papilar/patologia
Carcinoma Papilar/terapia
Seres Humanos
Achados Incidentais
Radioisótopos do Iodo/uso terapêutico
Masculino
Meia-Idade
Metástase Neoplásica/diagnóstico
Compostos Radiofarmacêuticos/uso terapêutico
Neoplasias da Glândula Tireoide/patologia
Neoplasias da Glândula Tireoide/terapia
Imagem Corporal Total/métodos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Iodine Radioisotopes); 0 (Radiopharmaceuticals)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171026
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008348


  5 / 2973 MEDLINE  
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[PMID]:28777832
[Au] Autor:Grammaticos PC; Antoniou DE
[Ad] Endereço:Hermou 51 str., P.C 54623, Thessaloniki, Makedonia, Greece. fgrammat@auth.gr.
[Ti] Título:Endless research II. The genomic era. Neohippocratic Medicine.
[So] Source:Hell J Nucl Med;20(2):107-109, 2017 May-Aug.
[Is] ISSN:1790-5427
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:The great progress of genetics research, during 2015-2017, will certainly influence all medical specialties including nuclear medicine. In nuclear medicine there are still problems to solve as to differentiate between infection, inflammation and cancer etc. Furthermore, in dosimetry and radiation protection there are worldwide problems. It has been reported that Cu-cetuximab immune-PET represented EGFR expression levels in ESCC tumors and that Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. Recent important research findings and few related suggestions for further research are mentioned related to Gastroenterology, Neohippocratic Medicine, the Respiratory System, Neurology and the Hayflick phenomenon. Perhaps we now live in the genetics transformation era, the Genomie's Era.
[Mh] Termos MeSH primário: Pesquisa em Genética
Neoplasias/genética
Neoplasias/radioterapia
Medicina Nuclear/tendências
Medicina de Precisão/tendências
Radioimunoterapia/tendências
[Mh] Termos MeSH secundário: Medicina Baseada em Evidências
Juramento Hipocrático
Seres Humanos
[Pt] Tipo de publicação:EDITORIAL
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE


  6 / 2973 MEDLINE  
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[PMID]:28658304
[Au] Autor:Kodaira S; Li HK; Konishi T; Kitamura H; Kurano M; Hasegawa S
[Ad] Endereço:Radiation Measurement Research Team, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
[Ti] Título:Validating α-particle emission from 211At-labeled antibodies in single cells for cancer radioimmunotherapy using CR-39 plastic nuclear track detectors.
[So] Source:PLoS One;12(6):e0178472, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently, 211At has received increasing attention as a potential radionuclide for cancer radioimmunotherapy. It is a α-particle emitter, which is extremely effective against malignant cells. We demonstrate a method to verify the efficiency of 211At-labeled trastuzumab antibodies (211At-trastuzumab) against HER2 antigens, which has not been determined for radioimmunotherapy. A CR-39 plastic nuclear detector is used for measuring the position and the linear energy transfer (LET) of individual 211At α- particle tracks. The tracks and 211At-trastuzumab-binding cells were co-visualized by using the geometric information recorded on the CR-39. HER2-positive human gastric cancer cells (NCI-N87), labelled with 211At-trastuzumab, were dropped on the centre of the CR-39 plate. Microscope images of the cells and the corresponding α-tracks acquired by position matching were obtained. In addition, 3.5 cm × 3.5 cm macroscopic images of the whole plate were acquired. The distribution of number of α-particles emitted from single cells suggests that 80% of the 211At-trastuzumab-binding cells emitted α-particles. It also indicates that the α-particles may strike the cells several times along their path. The track-averaged LET of the α-particles is evaluated to be 131 keV/µm. These results will enable quantitative evaluation of delivered doses to target cells, and will be useful for the in vitro assessment of 211At-based radioimmunotherapeutic agents.
[Mh] Termos MeSH primário: Partículas alfa/uso terapêutico
Anticorpos Monoclonais/uso terapêutico
Astato/química
Plásticos/química
Polietilenoglicóis/química
Radioimunoterapia/métodos
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Plastics); 25656-90-0 (CR 39); 30IQX730WE (Polyethylene Glycols); XI595HAL7H (Astatine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178472


  7 / 2973 MEDLINE  
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[PMID]:28566329
[Au] Autor:O'Steen S; Green DJ; Gopal AK; Orozco JJ; Kenoyer AL; Lin Y; Wilbur DS; Hamlin DK; Fisher DR; Hylarides MD; Gooley TA; Waltman A; Till BG; Press OW
[Ad] Endereço:Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. sosteen@fredhutch.org.
[Ti] Título:Venetoclax Synergizes with Radiotherapy for Treatment of B-cell Lymphomas.
[So] Source:Cancer Res;77(14):3885-3893, 2017 Jul 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Constitutive B-cell receptor signaling leads to overexpression of the antiapoptotic BCL-2 protein and is implicated in the pathogenesis of many types of B-cell non-Hodgkin lymphoma (B-NHL). The BCL-2 small-molecule inhibitor venetoclax shows promising clinical response rates in several lymphomas, but is not curative as monotherapy. Radiotherapy is a rational candidate for combining with BCL-2 inhibition, as DNA damage caused by radiotherapy increases the activity of pro-apoptotic BCL-2 pathway proteins, and lymphomas are exquisitely sensitive to radiation. We tested B-NHL responses to venetoclax combined with either external beam radiotherapy or radioimmunotherapy (RIT), which joins the selectivity of antibody targeting with the effectiveness of irradiation. We first tested cytotoxicity of cesium-137 irradiation plus venetoclax in 14 B-NHL cell lines representing five lymphoma subtypes. Combination treatment synergistically increased cell death in 10 of 14 lines. Lack of synergy was predicted by resistance to single-agent venetoclax and high BCL-XL expression. We then assessed the efficacy of external beam radiotherapy plus venetoclax in murine xenograft models of mantle cell (MCL), germinal-center diffuse large B-cell (GCB-DLBCL), and activated B-cell (ABC-DLBCL) lymphomas. In each model, external beam radiotherapy plus venetoclax synergistically increased mouse survival time, curing up to 10%. We finally combined venetoclax treatment of MCL and ABC-DLBCL xenografts with a pretargeted RIT (PRIT) system directed against the CD20 antigen. Optimal dosing of PRIT plus venetoclax cured 100% of mice with no detectable toxicity. Venetoclax combined with radiotherapy may be a promising treatment for a wide range of lymphomas .
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia
Linfoma de Células B/tratamento farmacológico
Linfoma de Células B/radioterapia
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Radioisótopos de Césio/farmacologia
Quimiorradioterapia
Feminino
Seres Humanos
Linfoma de Células B/imunologia
Camundongos
Camundongos Endogâmicos NOD
Tolerância a Radiação/efeitos dos fármacos
Radioimunoterapia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Cesium Radioisotopes); 0 (Sulfonamides); N54AIC43PW (venetoclax)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-17-0082


  8 / 2973 MEDLINE  
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[PMID]:28542406
[Au] Autor:Braster R; Grewal S; Visser R; Einarsdottir HK; van Egmond M; Vidarsson G; Bögels M
[Ad] Endereço:Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, The Netherlands.
[Ti] Título:Human IgG3 with extended half-life does not improve Fc-gamma receptor-mediated cancer antibody therapies in mice.
[So] Source:PLoS One;12(5):e0177736, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Current anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models. Nonetheless, no therapeutic human IgG3 mAbs have been developed due to the short in vivo half-life of most known IgG3 allotypes. In this manuscript, we compared the efficacy of V-gene matched IgG1 and IgG3 anti-tumour mAb (TA99) in mice, using natural variants of human IgG3 with short- or long half-life, differing only at position 435 with an arginine or histidine, respectively. RESULTS: In vitro human IgG1 and IgG3 did not show any differences in opsonisation ability of B16F10-gp75 mouse melanoma cells. IgG1, however, was superior in inducing phagocytosis of tumour cells by mouse macrophages. Similarly, in a mouse peritoneal metastasis model we did not detect an improved effect of IgG3 in preventing tumour outgrowth. Moreover, replacing the arginine at position 435 for a histidine in IgG3 to enhance half-life did not result in better suppression of tumour outgrowth compared to wild type IgG3 when injected prior to tumour cell injection. CONCLUSION: In conclusion, human IgG3 does not have improved therapeutic efficacy compared to human IgG1 in a mouse tumour model.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Imunoglobulina G/imunologia
Melanoma Experimental/imunologia
Monócitos/imunologia
Neoplasias Peritoneais/imunologia
Receptores de IgG/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/uso terapêutico
Citotoxicidade Celular Dependente de Anticorpos
Meia-Vida
Seres Humanos
Masculino
Melanoma Experimental/patologia
Melanoma Experimental/terapia
Camundongos
Camundongos Endogâmicos C57BL
Monócitos/patologia
Neoplasias Peritoneais/secundário
Neoplasias Peritoneais/terapia
Fagocitose
Radioimunoterapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (FCGR3A protein, human); 0 (Fc gamma receptor IIA); 0 (Immunoglobulin G); 0 (Receptors, IgG)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177736


  9 / 2973 MEDLINE  
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[PMID]:28514062
[Au] Autor:Li HK; Morokoshi Y; Nagatsu K; Kamada T; Hasegawa S
[Ad] Endereço:Radiation and Cancer Biology Team, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
[Ti] Título:Locoregional therapy with α-emitting trastuzumab against peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice.
[So] Source:Cancer Sci;108(8):1648-1656, 2017 Aug.
[Is] ISSN:1349-7006
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 ( At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α-particle radioimmunotherapy with At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of At-trastuzumab (1 MBq) was a more efficient means of delivery of At into metastatic tumors than i.v. injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA double-strand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with At-trastuzumab may offer a new treatment option for HER2-positive PMGC.
[Mh] Termos MeSH primário: Astato/química
Neoplasias Peritoneais/tratamento farmacológico
Neoplasias Peritoneais/secundário
Compostos Radiofarmacêuticos/administração & dosagem
Neoplasias Gástricas/tratamento farmacológico
Trastuzumab/administração & dosagem
[Mh] Termos MeSH secundário: Administração Intravenosa
Animais
Linhagem Celular Tumoral
Seres Humanos
Injeções Intraperitoneais
Camundongos
Neoplasias Peritoneais/metabolismo
Radioimunoterapia
Compostos Radiofarmacêuticos/química
Compostos Radiofarmacêuticos/farmacologia
Receptor ErbB-2/antagonistas & inibidores
Receptor ErbB-2/metabolismo
Neoplasias Gástricas/metabolismo
Distribuição Tecidual
Trastuzumab/química
Trastuzumab/farmacologia
Resultado do Tratamento
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radiopharmaceuticals); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); P188ANX8CK (Trastuzumab); XI595HAL7H (Astatine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1111/cas.13282


  10 / 2973 MEDLINE  
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[PMID]:28438082
[Au] Autor:Bourgeois M; Bailly C; Frindel M; Guerard F; Chérel M; Faivre-Chauvet A; Kraeber-Bodéré F; Bodet-Milin C
[Ad] Endereço:a Department of Nuclear Medicine , University Hospital , 44093 Nantes , France.
[Ti] Título:Radioimmunoconjugates for treating cancer: recent advances and current opportunities.
[So] Source:Expert Opin Biol Ther;17(7):813-819, 2017 Jul.
[Is] ISSN:1744-7682
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Radioimmunoconjugates have been used for 30 years to diagnose and treat cancer. For many years, the use of these therapeutic tools has been limited to haematological disorders, such as non-Hodgkin's lymphoma, given that they have only had a moderate effect on solid tumours. Areas covered: Recently, several strategies have revived the potential therapeutic application for radioimmunoconjugates. In this review, the authors review the advances in immunological engineering to develop new tools like monoclonal antibodies and their derivatives. Then, the authors summarize the development of radionuclides, the use of recombinant antibodies, pretargeting approaches, and dose fractionation techniques, providing opportunities for both therapeutic and diagnostic applications. Expert opinion: Radioimmunoconjugates used in nuclear medicine have entered a new era of development. These advances give rise to a variety of opportunities in the management of various cancers, where the radiolabelled antibodies may be particularly useful in immuno-specific phenotypic imaging e.g. companion diagnostics. Concerning therapeutic applications, radioimmunoconjugates have demonstrated their efficacy in the treatment of both haematological malignancies and solid tumours. Recent procedural developments are of great interest in optimising oncological targeted therapies. In the field of cancer theranostics, we believe that radioimmunoconjugated compounds are likely to play a large part in near future.
[Mh] Termos MeSH primário: Imunoconjugados/uso terapêutico
Neoplasias/terapia
Radioimunoterapia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/uso terapêutico
Seres Humanos
Imunoconjugados/química
Marcação por Isótopo
Neoplasias/diagnóstico
Neoplasias/imunologia
Tomografia por Emissão de Pósitrons
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Immunoconjugates)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1080/14712598.2017.1322577



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