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Bei der Castleman-Erkrankung handelt es sich um eine sehr seltene Erkrankung, die durch eine Hyperplasie des lymphatischen Gewebes gekennzeichnet ist. Die Atiologie ist zum Teil sehr unterschiedlich und umfasst neben autoimmunologischen, infektiologischen und autoinflammatorischen auch paraneoplastische Erkrankungen, beispielsweise eine monoklonale Gammopathie unklarer Signifikanz (MGUS) mit POEMS-Syndrom (Polyneuropathie, Organomegalie, Endokrinopathie, MGUS, „skin lesions“ [Hautveranderungen]). Allen gemein ist in der Regel eine Dysregulation/Uberproduktion bestimmter Zytokine und Wachstumsfaktoren (unter anderem Interleukin‑6 und „vascular endothelial growth factor“). In der Summe verursachen diese Veranderungen zum Teil eine sehr heterogene Symptomatik und erschweren damit haufig eine fruhzeitige Diagnose. Die Prognose der nicht erkannten und unbehandelten Erkrankung ist sehr ernst; die durchschnittliche 5‑Jahres-Uberlebensrate liegt bei 55–77 %. In der vorliegenden Arbeit wird der Fall eines 79-jahrigen Patienten mit therapierefraktarer Polyserositis beschrieben, bei dem nach > 8 Jahren die korrekte Diagnose gestellt wurde.

Monoclonal antibodies are extremely valuable functional biomaterials that are widely used not only in life science research but also in antibody drugs and test drugs. There is also a strong need to develop high-quality neutralizing antibodies as soon as possible in order to stop the rapid spread of new infectious diseases such as the SARS-CoV-2 virus. This study has developed a membrane-type immunoglobulin-directed hybridoma screening (MIHS) method for obtaining high-quality monoclonal antibodies with high efficiency and high speed. In addition to these advantages, this paper demonstrates that the MIHS method can selectively obtain monoclonal antibodies that specifically recognize the functional structure of proteins. The MIHS method is a useful technology that greatly contributes to the research community because it can be easily introduced in any laboratory that uses a flow cytometer.

ZusammenfassungEs wird über die erfolgreiche Behandlung des Rezidivs einer Anti-GBM-Erkrankung (assoziiert mit Antikörpern gegen die glomeruläre Basalmembran [GBM]) mittels Rituximab bei einem 17-jährigen Patienten berichtet. Die Nierenbiopsie mit Nachweis einer linearen Immunglobulin-G-Ablagerung entlang der Basalmembran stellt den Goldstandard dar, der von serologischen Analysen begleitet wird. Standardassays zur Anti-GBM-Bestimmung weisen hohe Raten an falsch-negativen Befunden auf. Eine Zunahme der Proteinurie trotz Standardtherapie mit Plasmapherese, Steroid und Cyclophosphamid war das klinische Korrelat des Erkrankungsrezidivs. Rituximab führte zu einer vollständigen Ausheilung.

To date, most antibodies recognizing the SARS-CoV-2 spike (S) protein target the receptor binding domain (RBD). Three recent studies (Cerutti et al., 2021; McCallum et al., 2021; and Suryadevara et al., 2021) report on highly protective antibodies that are specific to the N-terminal domain (NTD) and target a conserved supersite.

Covid-19 and the Media In this audio interview conducted on September 28, 2021, the editors are joined by former ProPublica president Dick Tofel to discuss Covid-19 coverage in the lay press, as we...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.

New Evidence on SARS-CoV-2 Vaccine Boosters In this audio interview conducted on September 14, 2021, the editors discuss new studies that measure the effectiveness of booster doses in raising antib...

SARS-CoV-2 and Immunosuppression In this article, the authors discuss the challenges of SARS-CoV-2 infection in patients with a weakened immune system, including the potential implications regardin...

This year also saw a great number of phase II and III studies presented at the ASCO Annual Meeting, in which new drugs (monoclonal antibodies, small molecules) were investigated as an alternative to or in combination with established mono- and polychemotherapy in patients with recurrences or distance metastases from head and neck squamous cell carcinoma (R/M-HNSCC). The studies now presented here describe the different concepts being applied to drug-based treatment of R/M-HNSCC and illustrate the variety of therapeutic approaches to treatment of recurrences and metastases.

OBJECTIVE The objective of this article was to conduct a systematic review of the treatment of moderate-to-severe asthma by administrating Dupilumab.METHODS A search on the online databases EBSCO, Scielo, PubMed, Medline Bireme, Lilacs, and The New England Journal of Medicine was conducted, publications from 2010 to 2018 were selected. The inclusion criteria were articles which contained control groups, tested the validity of Dupilumab, and verified the response of patients through controlled tests. For the search of such articles, the following keywords were used: “Dupilumab”, “asthma”, “Bronchial Asthma” AND “Asthma, Bronchial” AND their correspondent in Portuguese “asma”, “Asma brônquica” and “Asma brônquica”. The exclusion criteria were literature reviews, news, articles without control groups, articles on different subjects, Dupilumab studies on other diseases, articles concerning asthma without the use of Dupilumab, and repeated articles on the databases were discarded.RESULTS The literature considers that the medication shows a good response for the treatment of moderate-to-severe asthma and assists in the improvement of lung function, aside from resulting in few side effects. It presents good efficacy, safety, and tolerance by patients.CONCLUSIONS Dupilumab is promising for the treatment of asthma, whereas conventional therapy is deemed to be insufficient. More additional studies are needed to confirm the long-term safety and effectiveness., OBJETIVO Este artigo teve como objetivo fazer uma revisão sistemática sobre o tratamento da asma moderada a grave, administrando Dupilumabe.MÉTODOS Foi realizada uma busca nas plataformas on-line Ebsco, SciELO, PubMed, Medline Bireme, Lilacs e New England Journal of Medicine. Foram selecionadas publicações de 2010 a 2018 referentes a artigos que continham grupos controle, que testaram a validade de Dupilumabe e verificaram a resposta dos pacientes por meio de testes controlados. Para a busca desses artigos, foram utilizadas as seguintes palavras-chave: “Dupilumab”, “asthma”, “Bronchial Asthma” and “Asthma, Bronchial”. E o correspondente em português: “asma”, “Asma brônquica” and “Asma brônquica”. Os critérios de exclusão, revisões de literatura, notícias, artigos sem grupos de controle, artigos sobre diferentes assuntos, estudos de Dupilumabe sobre outras doenças, artigos sobre asma sem uso de Dupilumabe e artigos repetidos em plataformas de busca foram descartados. RESULTADOS A literatura aponta que a medicação apresenta boa resposta no tratamento da asma moderada a grave e auxilia na melhora da função pulmonar, além de resultar em poucos efeitos colaterais. Apresenta boa eficácia, segurança e tolerância pelos pacientes.CONCLUSÕES Dupilumabe é promissor para o tratamento da asma em que a terapia convencional se revela insuficiente. Maiores estudos adicionais são necessários para confirmar a segurança e a eficácia em longo prazo.

Points essentiels Les lymphomes a petites cellules non folliculaires regroupent plusieurs entites dont la description clinique et pathologique s’est affinee dans les 20 dernieres annees. Le lymphome du MALT, developpe aux depends du tissu lymphoide associe aux muqueuses, se manifeste par une atteinte d’organe en general isolee, mais une extension a distance peut exister. Certains patients atteints de lymphomes du MALT peuvent etre traites en eradiquant l’agent infectieux associe, tandis que le traitement local doit etre privilegie pour les autres cas ; et les formes disseminees et les patients en rechute relevent d’une association avec anticorps anti-CD20 et agent cytotoxique. Les patients atteints de lymphomes a cellules du manteau ont pu beneficier de nombreuses avancees, incluant l’utilisation de la cytarabine et de la bendamustine, les anticorps anti-CD20, les traitements intensifs (autogreffe) et dernierement une therapie ciblee (ibrutinib, inhibiteur de la tyrosine kinase de Bruton – BTK). Les patients atteints de lymphome de la zone marginale splenique ou ganglionnaire doivent etre evalues pour differentes options, parmi lesquelles l’immunochimiotherapie reste importante. Pour toutes ces entites, la mise en place des traitements pourra etre retardee de plusieurs annees pour certains groupes de patients. Bien que consideres comme incurables, le pronostic de ces pathologies s’est nettement ameliore et la majorite des patients pourront vivre de nombreuses annees avec des intervalles sans traitement souvent prolonges.

Hidradenitis suppurativa is a chronic immune mediated disease of universal distribution that causes great damage to the quality of life of the affected individual, whose prevalence is estimated at 0.41% in the Brazilian population. The objective of this work was update on physiopathogenesis, diagnosis and classification of hidradenitis suppurativa and to establish therapeutic recommendations in the Brazilian reality. It was organized as a work group composed of eight dermatologists from several institutions of the country with experience in the treatment of hidradenitis suppurativa and carried out review on the topic. Recommendations were elaborated and voted by modified Delphi system and statistical analysis of the results was performed. The Brazilian consensus on the clinical approach of hidradenitis suppurativa had the support of the Brazilian Society of Dermatology.

Die Rolle von Interleukin(IL)-17 im Rahmen der Pemphiguserkrankung ist nicht hinreichend geklart. Sowohl der Pemphigus vulgaris (PV) als auch der Pemphigus foliaceus (PF) weisen intralasional IL-17-positive Zellen auf. Eine Patientin mit zunachst vermuteter koinzidenter Psoriasis pustulosa (PP) und einem PF wurde mit dem Anti-IL-17-Antikorper Secukinumab behandelt. Der klinische Hautbefund verbesserte sich deutlich und die Anti-Desmoglein-1-Antikorper fielen deutlich ab. Bei Verlangerung des Injektionsintervalls von Secukinumab wurde jedoch ein erneuter Anstieg der Antikorper beobachtet. Wir vermuten einen dosisabhangigen Effekt von Secukinumab auf die Autoantikorperbildung beim PF. Ruckblickend besteht die Moglichkeit eines neutrophilen dominierten PF, der unter einer IL-17-Blockade zu einer annahernd vollstandigen Abheilung gekommen ist.

Resumen: Introducción: La proproteína convertasa subtilisina kexina tipo 9 (PCSK9) desempeña un papel importante en la modulación de los niveles plasmáticos de colesterol unido a las lipoproteínas de baja densidad (LDLC). La PCSK9 se une al receptor del LDLC (LDL[R]) perturba su reciclado endocítico y lo dirige a la degradación lisosomal. Por tanto, la activación de PCSK9 disminuye la expresión de los LDL(R) a nivel hepático e inhibe la captación de LDLC, lo que provoca hipercolesterolemia. Desarrollo: Hoy se sabe que diferentes polimorfismos de la PCSK9 se asocian a la aparición de ictus isquémico. Por otra parte, los fármacos inhibidores de PCSK9 inhiben la unión de PCSK9 con el LDL(R) y evitan la degradación del LDL(R) por lo que aumentan la captación hepática de LDLC, disminuyendo sus niveles en sangre.Diferentes estudios con anticuerpos monoclonales en fase 2 y 3 como el OSLER y el ODYSSEY LONG TERM han demostrado la eficacia y seguridad de los nuevos anticuerpos monoclonales contra PCSK9 como el evolucumab y alirocumab, y los primeros análisis exploratorios ya evidencian su eficacia en la disminución de eventos vasculares, incluidos los ictus. Conclusiones: Aunque el número de ictus recogidos en estos estudios ha sido bajo, en la actualidad existen varios ensayos centrados en resultados cardiovasculares en curso con evolocumab (estudio FOURIER), con alirocumab (estudio ODYSSEY OUTCOMES) y con bococizumab (estudios SPIRE-1 y SPIRE-2) que nos desvelarán el auténtico potencial de estos fármacos en la enfermedad cardiovascular y, en particular, en la prevención del ictus. Abstract: Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of plasma levels of low density lipoprotein cholesterol (LDLC). PCSK9 binds to the LDL receptor (LDLR), disrupts its endocytic recycling itinerary and directs it to lysosomal degradation. Activation of PCSK9 can thus decrease the expression of LDLR in the liver and inhibit LDL uptake, which leads to hypercholesterolaemia. Development: Currently we now know that different polymorphisms of PCSK9 are associated with the occurrence of ischaemic stroke. On the other hand, PCSK9 inhibitors prevent binding of PCSK9 to LDLR and inhibit degradation of LDLR, which results in increased hepatic uptake of LDL and lower LDL levels in blood.Different phase 2 and 3 studies, including OSLER and ODYSSEY LONG-TERM, have demonstrated the efficacy and safety of the new monoclonal antibodies against PCSK9 such as evolucumab and alirocumab, and the first exploratory analyses have shown evidence of their efficacy in decreasing vascular events, including stroke. Conclusions: Although few strokes have been reported by these studies, new ongoing trials examining the cardiovascular effects of evolucumab (FOURIER study), alirocumab (ODYSSEY OUTCOMES study), and bococizumab (SPIRE-1 and SPIRE-2 studies) will reveal the true potential of these drugs, particularly for the prevention of stroke. Palabras clave: Proproteína convertasa subtilisina kexina tipo 9, Inhibidores de PCSK9, Colesterol, LDL, Ictus, Prevención, Keywords: Pro-protein convertase subtilisin kexine type 9, PCSK9 inhibitors, Cholesterol, LDL, Stroke, Prevention

SARS-CoV-2 Spike-specific antibodies contribute the majority of the neutralizing activity in most convalescent human sera. Two SARS-CoV-2 variants, N501Y.V1 (also known as B.1.1.7 lineage or VOC-202012/01) and N501Y.V2 (B.1.351 lineage), reported from the United Kingdom and South Africa, contain several mutations in the receptor binding domain of Spike and are of particular concern. To address the infectivity and neutralization escape phenotypes potentially caused by these mutations, we used SARS-CoV-2 pseudovirus system to compare the viral infectivity, as well as the neutralization activities of convalescent sera and monoclonal antibodies (mAbs) against SARS-CoV-2 variants. Our results showed that N501Y Variant 1 and Variant 2 increase viral infectivity compared to the reference strain (wild-type, WT) in vitro. At 8 months after symptom onset, 17 serum samples of 20 participants (85%) retaining titers of ID50 >40 against WT pseudovirus, whereas the NAb titers of 8 samples (40%) and 18 samples (90%) decreased below the threshold against N501Y.V1 and N501Y.V2, respectively. In addition, both N501Y Variant 1 and Variant 2 reduced neutralization sensitivity to most (6/8) mAbs tested, while N501Y.V2 even abrogated neutralizing activity of two mAbs. Taken together the results suggest that N501Y.V1 and N501Y.V2 reduce neutralization sensitivity to some convalescent sera and mAbs.

By the end of 2020, more than 19 million Americans had received the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.1 Although a substantial proportion of these ...

Experiments with hybrid viruses are illuminating how SARS-CoV-2 can escape neutralizing antibodies.

ZusammenfassungEin Jahrhundert lang wurde die Serumtherapie von Seren tierischen Ursprungs und Hyperimmunglobulinen dominiert. Obwohl seit Ende der Achtzigerjahre des letzten Jahrhunderts zahlreiche monoklonale Antikörper (MAB) insbesondere zur Behandlung von immunologischen und onkologischen Erkrankungen entwickelt wurden, sollte es noch 20 Jahre bis zur Zulassung des ersten antiinfektiven MAB in der Europäischen Union dauern. In den folgenden 2 Dekaden kamen nur 2 weitere antiinfektive MAB hinzu. Interessanterweise werden zurzeit zur Bekämpfung der COVID-19-Pandemie zahlreiche MAB, die insbesondere in immunologischer Indikation zugelassen sind, zur Behandlung der Folgen der SARS-CoV-2-Infektion, wie Pneumonie oder Hyperimmunreaktion, eingesetzt.Im Folgenden werden die zugelassenen monoklonalen Antikörper zur Behandlung von Infektionskrankheiten vorgestellt. Darüber hinaus wird eine Übersicht über die aktuellen Entwicklungen, insbesondere bei der Therapie der SARS-CoV-2-Infektion, gegeben.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection (RTI) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which has been spreading worldwide This article is protected by copyright All rights reserved

Capitalizing on Immune Responses to Covid-19 In this audio interview conducted on May 20, 2020, the editors discuss recent advances involving convalescent plasma, monoclonal antibodies, and vaccine...

Human pharmacokinetics and internal radiation dosimetry of normal organs after injection with the 99mTc-labeled monoclonal antibody (intact and fragments) are simulated by the WinAct program and IDAC (Internal Dose Assessment by Computer) software. The WinAct program is used to calculate the cumulative activity in organs and tissues. The calculated cumulative activity is inputted to the IDAC software, an internal dosimetry program for nuclear medicine based on the International Commission on Radiological Protection (ICRP) adult reference voxel phantom, and the absorbed doses by the organs and tissues are estimated. The obtained absorbed doses for the 99mTc-labeled monoclonal antibody (intact and fragments) are compared with the published figures by ICRP-128. The WinAct program method to calculate the cumulative activity is more accurate, as the fraction distribution, Fs, is described and calculated for organs, not only for intake, as in the ICRP model, but also for elimination.

Resume Introduction Les inhibiteurs de point de controle immunitaire sont de plus en plus largement utilises dans la therapeutique anticancereuse avec une extension des indications. Leur toxicite est polymorphe, comprenant des atteintes dysimmunitaires specifiques d’organe et le developpement plus rare d’atteintes systemiques. Observations Nous rapportons 3 cas de granulomatose sarcoidosique developpee durant un traitement par inhibiteurs de point de controle immunitaire (dans des tumeurs primitives differentes : adenocarcinome bronchique, cancer bronchique a petites cellules et melanome). La presentation radioclinique et la gravite de l’atteinte etaient variables. Le diagnostic reposait sur l’examen anatomo-pathologique et l’elimination des diagnostics differentiels, notamment infectieux. Dans ce cas, l’immunotherapie doit etre stoppee et sa re-administration ulterieure reste a determiner. Une corticotherapie systemique est discutee selon l’intensite des symptomes. Conclusions La connaissance de cette toxicite est primordiale car les signes clinico-radiologiques peuvent faire evoquer une progression tumorale.

Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name ‘biosimilar’. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

Drug development for the treatment of Alzheimer's disease (AD) has been for a long time focused on agents that were expected to support endogenous β-amyloid (Aβ) in a monomeric state and destroy soluble Aβ oligomers and insoluble Aβ aggregates. However, this strategy has failed over the last 20 years and was eventually abandoned. In this review, we propose a new approach to the anti-amyloid AD therapy based on the latest achievements in understanding molecular causes of cerebral amyloidosis in AD animal models.

New promising treatment options for chronic inflammatory bowel diseases, confirm the expanded pathophysiological understanding in terms of the interactions of the gastrointestinal microbiome with the adaptive and innate immune response and barrier protection. Therefore, these interrelations are focus of research and therapeutic strategies. The following review will give insights into the pathomechanisms, current treatment options and future developments.

Breast cancer (BC) is the most common cancer diagnosed among women. The development of new personalized therapeutic strategies has reshaped the landscape in this field. However, BC is still the first cause of death among women. Interestingly, several preclinical studies and some clinical evidences are focused their attention on the role of immune system and immunotherapy on cancer control, also in BC. Areas covered: Usually, BC has been considered a not immunogenic tumor for its low mutational load. However, recent studies have evidenced that some subtypes, triple negative and HER-2 positive BC, are 'hot' tumors, thus more immunogenic. Moreover, the presence of immune infiltrate is positively associated with favorable prognosis. Therefore, the use of immune-checkpoint inhibitors seems to be an encouraging treatment option also in BC. Among these drugs, atezolizumab is an anti-PD-L1 monoclonal antibody with a particular structure that reduce antibody-dependent cellular cytotoxicity against T cells, increasing quantitatively and qualitatively the effective response. Expert opinion: The use of immunotherapy is a promising option for BC. However, at the same time it still raises many doubts. Surely, the research and the validation of immune biomarkers can permit to identify patients who more benefit from these drugs.

Charge heterogeneity is often evaluated during biosimilar development as it is a universal feature of monoclonal antibodies (mAbs). A common approach in the industry is to develop a biosimilar product with a similar overall charge profile as the reference product. However, uncertainty remains with this approach as the same charge profile in two different products may be caused by different mechanisms. In this work, we present a comprehensive investigation of the charge variants of a therapeutic monoclonal antibody and its biosimilar candidate. Not only did the candidate show a similar charge profile as the reference product, our studies revealed that the same factors contributed to the charge variants of the reference product and the biosimilar candidate. We believe our cause-based approach mitigates the risks associated with the profile-based method and is a rational approach for the charge evaluation of biosimilars.

Fluorescence-guided imaging during surgery is a promising technique that is increasingly used to aid surgeons in identifying sites of tumor and surgical margins. Of the two types of fluorescent probes, always-on and activatable, activatable probes are preferred because they produce higher target-to-background ratios, thus improving sensitivity compared with always on probes that must contend with considerable background signal. There are two types of activatable probes: 1) enzyme-reactive probes that are normally quenched but can be activated after cleavage by cancer-specific enzymes (activity-based probes) and 2) molecular-binding probes which use cancer targeting moieties such as monoclonal antibodies to target receptors found in abundance on cancers and are activated after internalization and lysosomal processing (binding-based probes). For fluorescence-guided intraoperative surgery, enzyme-reactive probes are superior because they can react quickly, require smaller dosages especially for topical applications, have limited side effects, and have favorable pharmacokinetics. Enzyme-reactive probes are easier to use, fit better into existing work flows in the operating room and have minimal toxicity. Although difficult to prove, it is assumed that the guidance provided to surgeons by these probes results in more effective surgeries with better outcomes for patients. In this review, we compare these two types of activatable fluorescent probes for their ease of use and efficacy.

Resume Introduction La prise en charge classique des cancers bronchiques non a petites cellules de stade avance ou metastatique reposait essentiellement sur la chimiotherapie cytotoxique pour les tumeurs sans mutation oncogenique ciblable avec des resultats modestes en termes de gain de survie. Etat des connaissances La comprehension de mecanismes impliques dans le controle du systeme immunitaire a abouti au developpement d’anticorps diriges contre certains points de controle comme PD-L1. Les premiers resultats cliniques encourageants des anticorps monoclonaux diriges contre PD1 ou PD-L1 objectives en etude de phase I ont ete confirmes dans plusieurs etudes randomisees de phase III. Conclusion Ces nouveaux medicaments constituent maintenant un standard therapeutique en seconde ligne metastatique et a l’avenir, a tout le moins pour le pembrolizumab, en 1re ligne. Leur interet en adjuvant apres un traitement locoregional a visee curative est en cours d’investigation.

Fil: Jaworski, Juan Pablo. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Virologia E Innovaciones Tecnologicas. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Virologia E Innovaciones Tecnologicas.; Argentina