DOCSLIB.ORG

Monoclonal Antibodies in Asthma Therapy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Monoclonal Antibodies in Asthma Therapy MonoclonalMonoclonal AntibodiesAntibodies inin AsthmaAsthma TherapyTherapy YehiaYehia ElEl --GamalGamal MD,MD, PhDPhD ConflictConflict ofof InterestInterest NothingNothing toto disclosedisclose ObjectivesObjectives FollowingFollowing thisthis presentation,presentation, thethe audienceaudience shouldshould bebe ableable to:to: ••RecognizeRecognize somesome importantimportant monoclonalmonoclonal antibodiesantibodies availableavailable forfor asthmaasthma therapy.therapy. ••IdentifyIdentify candidatescandidates forfor treatmenttreatment withwith monoclonalmonoclonal antibodies.antibodies. ••BeBe awareaware ofof thethe sideside effectseffects andand costcost -- benefitbenefit ofof suchsuch therapy.therapy. SinceSince thethe firstfirst publicationpublication byby KohlerKohler andand MilsteinMilstein onon thethe productionproduction ofof murinemurine monoclonalmonoclonal antibodiesantibodies (MAbs)(MAbs) byby hybridomahybridoma technology,technology, therapeutictherapeutic useuse ofof MAbsMAbs hashas becomebecome aa majormajor partpart ofof treatmentstreatments inin variousvarious diseases.diseases. Köhler G, Milstein C. Nature 1975;256: http://en.wikipedia.org/wiki/Mon 495 -7. oclonal_antibodies SchematicSchematic representationrepresentation ofof MAbMAb productionproduction Martin -Mateos MA. Allergol Immunopathol (Madr) 2007; 35(4):145 -50. MAbsMAbs inin allergicallergic diseasesdiseases (cont(cont ’’d)d) OmalizumabOmalizumab (anti(anti --IgEIgE ab)ab) •• ItIt isis aa recombinantrecombinant humanizedhumanized monoclonalmonoclonal antibodyantibody (rhuMAb(rhuMAb --E25)E25) developeddeveloped byby immunizingimmunizing micemice withwith humanhuman IgE.IgE. •• Then,Then, aa monoclonalmonoclonal antibodyantibody waswas selectedselected thatthat recognizesrecognizes IgEIgE atat thethe samesame sitesite asas thethe highhigh --affinityaffinity receptorreceptor forfor IgEIgE (Fc(Fc εεRI).RI). Milgrom H, et al. N Engl J Med 1999;341(26):1966 -73. MAbsMAbs inin allergicallergic diseasesdiseases (cont(cont ’’d)d) OmalizumabOmalizumab isis thethe onlyonly MAbMAb toto datedate thatthat hashas beenbeen foundfound toto bebe effectiveeffective andand approvedapproved byby bothboth thethe FDAFDA andand EuropeanEuropean MedicinesMedicines AgencyAgency (EMEA)(EMEA) forfor thethe treatmenttreatment ofof difficultdifficult allergicallergic asthma.asthma. Bousquet J, et al. Expert Opin Biol Ther 2008;8(12):1921 -8. MechanismsMechanisms ofof ActionAction ofof OmalizumabOmalizumab •• ReducesReduces serumserum levelslevels ofof freefree IgEIgE •• DownDown --regulatesregulates expressionexpression ofof IgEIgE receptorsreceptors (FceRI)(FceRI) onon mastmast cellscells andand basophils.basophils. •• InIn thethe airwaysairways ofof patientspatients withwith allergicallergic asthma,asthma, itit reducesreduces FcFc εεRI+RI+ andand IgE+IgE+ cellscells andand causescauses aa profoundprofound reductionreduction inin tissuetissue eosinophilia,eosinophilia, togethertogether withwith reductionsreductions inin submucosalsubmucosal TT --cellcell andand BB --cellcell numbers.numbers. Holgate S, Casale T, Wenzel S, Bousquet J, Deniz Y, Reisner C. J Allergy Clin Immunol 2005;115(3):459 -65. MechanismsMechanisms ofof actionaction ofof omalizumabomalizumab (cont(cont ’’d)d) •• TheThe reductionsreductions inin circulatingcirculating levelslevels ofof IgEIgE resultingresulting fromfrom omalizumabomalizumab treatmenttreatment leadsleads toto reductionsreductions inin FceRIFceRI expressionexpression onon mastmast cells,cells, basophilsbasophils andand dendriticdendritic cells.cells. •• ThisThis combinedcombined effecteffect resultsresults inin attenuationattenuation ofof severalseveral markersmarkers ofof inflammation,inflammation, includingincluding peripheralperipheral andand bronchialbronchial tissuetissue eosinophilia,eosinophilia, levelslevels ofof GMGM --CSF,CSF, ILIL --2,2, ILIL --4,4, ILIL --55 andand ILIL --13.13. •• ItIt maymay alsoalso reducereduce allergenallergen presentationpresentation toto TT -- cellscells andand thethe productionproduction ofof Th2Th2 cytokines.cytokines. Holgate S, et al. Allergy 2009:64(12):1728 –36. Fig 2 ProposedProposed MechanismsMechanisms ofof ActionAction ofof OmalizumabOmalizumab Source: Journal Holgateof Allergy and ClinOI:10.1016/j.jac S, et al.i.2004.11.053 J Allergy ) Clin Immunol 2005;115(3):459 -65. TreatmentTreatment ofof allergicallergic asthmaasthma withwith monoclonalmonoclonal antianti --IgEIgE antibody:antibody: rhuMAbrhuMAb --E25E25 StudyStudy Group.Group. Serum concentrations of total and free IgE in subjects given a low dose of rhuMAb -E25 for 20 weeks Milgrom H, et al. N Engl J Med. 1999 Dec 23;341(26):1966 -73. Fig 1 ImmunohistochemicalImmunohistochemical stainingstaining ofof bronchialbronchial biopsybiopsy specimensspecimens beforebefore (( leftleft )) andand afterafter (( rightright )) 1616 weeksweeks ofof omalizumabomalizumab treatment.treatment. RepresentativeRepresentative sectionssections showshow stainingstaining withwith antibodyantibody against:against: ECPECP (A(A andand B)B) CellCell --surfacesurface IgEIgE (C(C andand D)D) HighHigh --affinityaffinity IgEIgE RR (E(E andand F)F) ILIL --44 (G(G andand H)H) Djukanovi ć R, et al. Am J Respir Crit Care Med 2004;170:583 -93. Fig 1 EosinophilEosinophil apoptosisapoptosis atat baselinebaseline andand weekweek 1212 ofof omalizumabomalizumab therapy:therapy: TheThe omalizumabomalizumab groupgroup (n(n == 9)9) demonstrateddemonstrated aa significantsignificant increaseincrease inin AnnexinAnnexin --positivepositive eosinophilseosinophils comparedcompared withwith placeboplacebo (n(n == 10).10). ∗∗ ∗∗∗∗ ∗∗∗∗pp << 0.010.01 Noga O,et al. J Allergy Clin Immunol 2006;117:1493 –9. Individual eosinophil counts at baseline and after 12 weeks of treatment with omalizumab or placebo. Horizontal bars represent median values van Rensen E, et al. Allergy 2009;64:72 –80. ForcedForced expiratoryexpiratory volumevolume inin 11 secondsecond asas aa percentagepercentage ofof baselinebaseline inin thethe placeboplacebo (A)(A) andand omalizumabomalizumab (B)(B) groups.groups. van Rensen E, et al. Allergy 2009;64:72 –80. EffectEffect ofof addadd --onon therapytherapy withwith omalizumabomalizumab inin patientspatients withwith severesevere persistentpersistent asthmaasthma whosewhose asthmaasthma waswas inadequatelyinadequately controlledcontrolled byby therapytherapy withwith highhigh --dosedose ICSsICSs plusplus aa LABALABA Humbert M, et al. Allergy 2005; 60:309 –16 AntiAnti --IgEIgE TherapyTherapy inin ChildrenChildren •• OmalizumabOmalizumab isis approvedapproved forfor thethe treatmenttreatment ofof adultsadults andand adolescentsadolescents (12(12 years)years) withwith inadequatelyinadequately controlledcontrolled moderatemoderate --toto --severesevere (United(United States)States) oror severesevere (Europe)(Europe) allergicallergic (IgE(IgE -- mediated)mediated) asthma.asthma. http://www.xolair.com/prescribing_information.html. http://www.emea.europa.eu/humandocs/Humans/EPAR/xolair/xolair.ht m. •• AA randomizedrandomized DBPCDBPC studystudy inin 334334 childrenchildren (6(6 toto 1212 years)years) withwith moderatemoderate --toto --severesevere allergicallergic asthma,asthma, omalizumabomalizumab significantlysignificantly reducedreduced asthmaasthma exacerbationsexacerbations andand enabledenabled reductionsreductions inin ICSICS dose.dose. Milgrom H, et al. Pediatrics 2001;108:E36. AntiAnti --IgEIgE TherapyTherapy inin ChildrenChildren (cont(cont ’’d)d) MoreMore recently,recently, LanierLanier etet al.al. demonstrated,demonstrated, inin aa RDBPCRDBPC trial,trial, thatthat addadd --onon therapytherapy withwith omalizumabomalizumab hashas aa reassuringreassuring safetysafety profile,profile, withwith nono increasedincreased riskrisk ofof adverseadverse events,events, andand reducesreduces asthmaasthma exacerbationsexacerbations inin childrenchildren ((66 toto <12<12 yearsyears )) withwith inadequatelyinadequately controlledcontrolled moderatemoderate --toto -- severesevere allergicallergic asthma.asthma. Lanier B, et al. J Allergy Clin Immunol 2009;124:1210 -6. Fig 2 ClinicallyClinically significantsignificant asthmaasthma exacerbationexacerbation ratesrates overover aa periodperiod ofof 2424 weeksweeks (primary(primary outcome;outcome; A)A) andand 5252 weeksweeks (B)(B) inin patientspatients withwith moderatemoderate --toto -- severesevere asthmaasthma treatedtreated withwith addadd --onon omalizumabomalizumab Lanier B , et al. J Allergy Clin Immunol 2009;124(6):1210 -6. AsthmaAsthma symptomsymptom rere --emergenceemergence afterafter omalizumabomalizumab withdrawalwithdrawal •• TheThe reasonreason forfor omalizumabomalizumab beingbeing ineffectiveineffective inin somesome patientspatients isis unknown,unknown, butbut itit isis reasonablereasonable toto askask whetherwhether thethe ‘‘‘‘ failuresfailures ’’’’ resultresult fromfrom ineffectiveineffective reductionsreductions inin IgEIgE levels.levels. •• QuestionsQuestions areare beingbeing askedasked aboutabout whetherwhether thethe dosedose cancan bebe reducedreduced afterafter monthsmonths ofof treatmenttreatment oror whetherwhether offoff --tabletable regimensregimens cancan bebe used.used. •• ReducingReducing omalizumabomalizumab dosesdoses maymay resultresult inin increaseincrease inin freefree IgEIgE causingcausing deteriorationdeterioration inin asthmaasthma control.control. Salvin RG, et al. J Allergy Clin Immunol 2009;123(1):107 -13. MacGlashan D. J Allergy Clin Immunol 2009;123(1):114 -5. OmalizumabOmalizumab SafetySafety
Load more

Recommended publications
  • BAFF-Neutralizing Interaction of Belimumab Related to Its Therapeutic Efficacy for Treating Systemic Lupus Erythematosus
    ARTICLE DOI: 10.1038/s41467-018-03620-2 OPEN BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus Woori Shin1, Hyun Tae Lee1, Heejin Lim1, Sang Hyung Lee1, Ji Young Son1, Jee Un Lee1, Ki-Young Yoo1, Seong Eon Ryu2, Jaejun Rhie1, Ju Yeon Lee1 & Yong-Seok Heo1 1234567890():,; BAFF, a member of the TNF superfamily, has been recognized as a good target for auto- immune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by the FDA for use in treating systemic lupus erythematosus. However, the molecular basis of BAFF neutralization by belimumab remains unclear. Here our crystal structure of the BAFF–belimumab Fab complex shows the precise epitope and the BAFF-neutralizing mechanism of belimumab, and demonstrates that the therapeutic activity of belimumab involves not only antagonizing the BAFF–receptor interaction, but also disrupting the for- mation of the more active BAFF 60-mer to favor the induction of the less active BAFF trimer through interaction with the flap region of BAFF. In addition, the belimumab HCDR3 loop mimics the DxL(V/L) motif of BAFF receptors, thereby binding to BAFF in a similar manner as endogenous BAFF receptors. Our data thus provides insights for the design of new drugs targeting BAFF for the treatment of autoimmune diseases. 1 Department of Chemistry, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. 2 Department of Bio Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. These authors contributed equally: Woori Shin, Hyun Tae Lee, Heejin Lim, Sang Hyung Lee.
    [Show full text]
  • Xolair/Omalizumab
    Therapeutic/Humanized Antibodies ELISA Kits ‘Humanized antibodies” are ‘Animal Antibodies’ that have been modified by recombinant DNA-technology to reduce the overall content of the animal- portion of immunoglobulin so as to increase acceptance by humans or minimize ‘rejection’. By analogy, if the hands of a mouse is actually responsible for grabbing things then ‘humanized-mouse’ will only contain the ‘mouse hands’ and the rest of the body will be human. Since the size of the IgGs is similar in mouse and human, the size of the native mouse IgG and the ‘humanized IgG’ does not significantly change. Antigen recognition property of an antibody actually resides in small portion of the IgG molecule called the ‘antigen binding site or Fab’. Therefore, humanized antibodies contain the minimal portion from the Fab or the epitopes necessary for antigen binding. The process of "humanization of antibodies" is usually applied to animal (mouse) derived monoclonal antibodies for therapeutic use in humans (for example, antibodies developed as anti-cancer drugs). Xolair (Anti-IgE) is an example of humanized IgG. The portion of the mouse IgG that remains in the ‘humanized IgG’ may be recognized as foreign by humans and may result into the generation of “Human Anti-Drug Antibodies (HADA). The presence of anti-Drug antibody (e.g., Human Anti-Rituximab IgG) that may limit the long-term usage the humanized antibody (Rituximab). Not all monoclonal antibodies designed for human therapeutic use need be humanized since many therapies are short-term. The International Nonproprietary Names of humanized antibodies end in “-zumab”, as in “omalizumab”. Humanized antibodies are distinct from chimeric or fusion antibodies.
    [Show full text]
  • Cytokine Nomenclature
    RayBiotech, Inc. The protein array pioneer company Cytokine Nomenclature Cytokine Name Official Full Name Genbank Related Names Symbol 4-1BB TNFRSF Tumor necrosis factor NP_001552 CD137, ILA, 4-1BB ligand receptor 9 receptor superfamily .2. member 9 6Ckine CCL21 6-Cysteine Chemokine NM_002989 Small-inducible cytokine A21, Beta chemokine exodus-2, Secondary lymphoid-tissue chemokine, SLC, SCYA21 ACE ACE Angiotensin-converting NP_000780 CD143, DCP, DCP1 enzyme .1. NP_690043 .1. ACE-2 ACE2 Angiotensin-converting NP_068576 ACE-related carboxypeptidase, enzyme 2 .1 Angiotensin-converting enzyme homolog ACTH ACTH Adrenocorticotropic NP_000930 POMC, Pro-opiomelanocortin, hormone .1. Corticotropin-lipotropin, NPP, NP_001030 Melanotropin gamma, Gamma- 333.1 MSH, Potential peptide, Corticotropin, Melanotropin alpha, Alpha-MSH, Corticotropin-like intermediary peptide, CLIP, Lipotropin beta, Beta-LPH, Lipotropin gamma, Gamma-LPH, Melanotropin beta, Beta-MSH, Beta-endorphin, Met-enkephalin ACTHR ACTHR Adrenocorticotropic NP_000520 Melanocortin receptor 2, MC2-R hormone receptor .1 Activin A INHBA Activin A NM_002192 Activin beta-A chain, Erythroid differentiation protein, EDF, INHBA Activin B INHBB Activin B NM_002193 Inhibin beta B chain, Activin beta-B chain Activin C INHBC Activin C NM005538 Inhibin, beta C Activin RIA ACVR1 Activin receptor type-1 NM_001105 Activin receptor type I, ACTR-I, Serine/threonine-protein kinase receptor R1, SKR1, Activin receptor-like kinase 2, ALK-2, TGF-B superfamily receptor type I, TSR-I, ACVRLK2 Activin RIB ACVR1B
    [Show full text]
  • Infliximab, Adalimumab and Golimumab for Treating Moderately
    HEALTH TECHNOLOGY ASSESSMENT VOLUME 20 ISSUE 39 MAY 2016 ISSN 1366-5278 Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model Rachel Archer, Paul Tappenden, Shijie Ren, Marrissa Martyn-St James, Rebecca Harvey, Hasan Basarir, John Stevens, Christopher Carroll, Anna Cantrell, Alan Lobo and Sami Hoque DOI 10.3310/hta20390 Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model Rachel Archer,1* Paul Tappenden,1 Shijie Ren,1 Marrissa Martyn-St James,1 Rebecca Harvey,1 Hasan Basarir,1 John Stevens,1 Christopher Carroll,1 Anna Cantrell,1 Alan Lobo2 and Sami Hoque3 1Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK 2Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK 3Barts Health NHS Trust, London, UK *Corresponding author Declared competing interests of authors: none Published May 2016 DOI: 10.3310/hta20390 This report should be referenced as follows: Archer R, Tappenden P, Ren S, Martyn-St James M, Harvey R, Basarir H, et al. Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model. Health Technol Assess 2016;20(39). Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE, Excerpta Medica/EMBASE, Science Citation Index Expanded (SciSearch®) and Current Contents®/ Clinical Medicine.
    [Show full text]
  • Kate Fitzgerald
    In This Issue: 2020 Young Investigator Awardees pg. 3-9 In Memorium page pg. 14-15 New Member Mini-Bios pg. 19-21 Trials of Interferon Lambda pg. 31 Cytokines 2021 Hybrid Meetin pg. 24-27 Signals THE INTERNATIONAL CYTOKINE & INTERFERON SOCIETY + NEWSLETTER APRIL 2021 I VOLUME 9 I NO. 1 A NOTE FROM THE ICIS PRESIDENT Kate Fitzgerald Dear Colleagues, Greetings from the International Cytokine and Interferon Society! I hope you and your family are staying safe during these still challenging times. Thankfully 2020 is behind us now. We have lived through the COVID-19 pandemic, an event that will continue to impact our lives for some time and likely alter how we live in the future. Despite the obvious difficulties of this past year, I can’t help but marvel at the scientific advances that have been made. With everything from COVID-19 testing, to treatments and especially to the rapid pace of vaccine development, we are so better off today than even a few months back. The approval of remarkably effective COVID-19 vaccines now rolling out in the US, Israel, UK, Europe and across the globe, brings light at the end of the tunnel. The work of many of you has helped shape our understanding of the host response to Sars-CoV2 and the ability of this virus to limit antiviral immunity while simultaneously driving a cytokine driven hyperinflammatory response leading to deadly consequences for patients. The knowledge gained from all of your efforts has been put to good use to stem the threat of this deadly virus.
    [Show full text]
  • (Human) ELISA Kit Rev 06/20 (Catalog # E 4381 - 100, 100 Assays, Store at 4°C) I
    FOR RESEARCH USE ONLY! TM BioSim Omalizumab (Human) ELISA Kit rev 06/20 (Catalog # E4381-100, 100 assays, Store at 4°C) I. Introduction: Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FceRI) on the surface of mast cells and basophils. Reduction in surface-bound IgE on FceRI-bearing cells limits the degree of release of mediators of the allergic response. Omalizumab is used to treat severe, persistent asthma. BioSimTM Omalizumab ELISA kit has been developed for specific quantification of Omalizumab concentration in human serum or plasma with high sensitivity and reproducibility. II. Application: This ELISA kit is used for in vitro quantitative determination of Omalizumab Detection Range: 10 - 1000 ng/ml Sensitivity: 10 ng/ml Assay Precision: Intra-Assay: CV < 15%; Inter-Assay: CV < 15% (CV (%) = SD/mean X 100) Recovery rate: 85 – 115% with normal human serum samples with known concentrations Cross Reactivity: There is no cross reaction with native serum immunoglobulins and tested monoclonal antibodies such as infliximab (Remicade®), adalimumab (Humira®), etanercept (Enbrel®), bevacizumab, trastuzumab III. Sample Type: Human serum and plasma IV. Kit Contents: Components E4381-100 Part No. Micro ELISA Plate 1 plate E4381-100-1 Omalizumab Standards (S1 – S7) 1 ml X 7 E4381-100-2.x Assay Buffer 50 ml E4381-100-3 HRP-conjugate Probe 12 ml E4381-100-4 TMB substrate (Avoid light) 12 ml E4381-100-5 Stop Solution 12 ml E4381-100-6 Wash buffer (20X) 50 ml E4381-100-7 Plate sealers 2 E4381-100-8 V.
    [Show full text]
  • (Human) ELISA Kit Rev 07/18 (Catalog # E 4398 - 100, 100 Assays, Store at 4°C) I
    FOR RESEARCH USE ONLY! TM BioSim anti-Ipilimumab (Yervoy®) (Human) ELISA Kit rev 07/18 (Catalog # E4398-100, 100 assays, Store at 4°C) I. Introduction: Ipilimumab (Yervoy®) is a fully human IgG1κ antibody that binds to CTLA-4 (cytotoxic T lymphocyteassociated antigen 4), a molecule on T- cells that is indicated for unresectable or metastatic melanoma. The absence or presence of CTLA-4 can augment or suppress the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells. The proposed mechanism of action is indirect, and may be through T-cell - mediated anti-tumor immune responses. However, some patients develop unwanted immunogenicity, which leads to production of anti-drug-antibodies (ADAs) inactivating the therapeutic effects of the treatment and, in rare cases, inducing adverse effects. BioVision’s BioSimTM anti-Ipilimumab ELISA kit is designed to detect antibody against Ipilimumab with high specificity and sensitivity in biological matrices. II. Application: This ELISA kit is used for in vitro qualitative determination of antibody against Ipilimumab in serum and plasma Cross Reactivity: Ipilimumab (Yervoy®) infusion camouflages/masks the presence of antibody to Ipilimumab (ATP) in serum/plasma samples. Therefore, blood sampling time is critical for detection of ATP. It is convenient to obtain blood sample just before the infusion or at least 2 weeks after the infusion of Ipilimumab. III. Sample Type: Human serum and plasma IV. Kit Contents: Components E4398-100 Part No. Micro ELISA Plate 1 plate E4398-100-1 Positive Control 0.25 ml E4398-100-2 Negative Control 0.5 ml E4398-100-3 Assay Buffer 12 ml E4398-100-4 Peroxidase Conjugate 12 ml E4398-100-5 TMB substrate (Avoid light) 12 ml E4398-100-6 Stop Solution 12 ml E4398-100-7 Wash buffer (20X) 50 ml E4398-100-8 Plate sealers 2 E4398-100-9 V.
    [Show full text]
  • Pulmonary Delivery of Biological Drugs
    pharmaceutics Review Pulmonary Delivery of Biological Drugs Wanling Liang 1,*, Harry W. Pan 1 , Driton Vllasaliu 2 and Jenny K. W. Lam 1 1 Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China; [email protected] (H.W.P.); [email protected] (J.K.W.L.) 2 School of Cancer and Pharmaceutical Sciences, King’s College London, 150 Stamford Street, London SE1 9NH, UK; [email protected] * Correspondence: [email protected]; Tel.: +852-3917-9024 Received: 15 September 2020; Accepted: 20 October 2020; Published: 26 October 2020 Abstract: In the last decade, biological drugs have rapidly proliferated and have now become an important therapeutic modality. This is because of their high potency, high specificity and desirable safety profile. The majority of biological drugs are peptide- and protein-based therapeutics with poor oral bioavailability. They are normally administered by parenteral injection (with a very few exceptions). Pulmonary delivery is an attractive non-invasive alternative route of administration for local and systemic delivery of biologics with immense potential to treat various diseases, including diabetes, cystic fibrosis, respiratory viral infection and asthma, etc. The massive surface area and extensive vascularisation in the lungs enable rapid absorption and fast onset of action. Despite the benefits of pulmonary delivery, development of inhalable biological drug is a challenging task. There are various anatomical, physiological and immunological barriers that affect the therapeutic efficacy of inhaled formulations. This review assesses the characteristics of biological drugs and the barriers to pulmonary drug delivery.
    [Show full text]
  • Cimzia (Certolizumab Pegol) AHM
    Cimzia (Certolizumab Pegol) AHM Clinical Indications • Cimzia (Certolizumab Pegol) is considered medically necessary for adult members 18 years of age or older with moderately-to-severely active disease when ALL of the following conditions are met o Moderately-to-severely active Crohn's disease as manifested by 1 or more of the following . Diarrhea . Abdominal pain . Bleeding . Weight loss . Perianal disease . Internal fistulae . Intestinal obstruction . Megacolon . Extra-intestinal manifestations: arthritis or spondylitis o Crohn's disease has remained active despite treatment with 1 or more of the following . Corticosteroids . 6-mercaptopurine/azathioprine • Certollizumab pegol (see note) is considered medically necessary for persons with active psoriatic arthritis who meet criteria in Psoriasis and Psoriatic Arthritis: Biological Therapies. • Cimzia, (Certolizumab Pegol), alone or in combination with methotrexate (MTX), is considered medically necessary for the treatment of adult members 18 years of age or older with moderately-to-severely active rheumatoid arthritis (RA). • Cimzia (Certolizumab pegol is considered medically necessary for reducing signs and symptoms of members with active ankylosing spondylitis who have an inadequate response to 2 or more NSAIDs. • Cimzia (Certolizumab Pegol) is considered investigational for all other indications (e.g.,ocular inflammation/uveitis; not an all-inclusive list) because its effectiveness for indications other than the ones listed above has not been established. Notes • There are several brands of targeted immune modulators on the market. There is a lack of reliable evidence that any one brand of targeted immune modulator is superior to other brands for medically necessary indications. Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Simponi (golimumab), Simponi Aria (golimumab intravneous), and Stelara (ustekinumab) brands of targeted immune modulators ("least cost brands of targeted immune modulators") are less costly to the plan.
    [Show full text]
  • Infliximab Infusion (Page 1 of 2)
    Patient Name: _________________ Provider Orders for: DOB: ________________ InFLIXimab Infusion (Page 1 of 2) = must check off to order / automatically initiated unless crossed out Date: ____________ Time: _________ Weight _______kg Height: _______cm BSA: __________ Diagnosis: Crohn’s disease Ulcerative colitis Plaque psoriasis Psoriatic arthritis Rheumatoid arthritis Ankylosing spondylitis PPD Date: ____________ Result: __________ Chest X-Ray Date: _______ Result: __________ Infusion: Inflectra (Drug of choice) Remicade (Non-formulary – Provider must complete a formulary request form) Infusion Frequency: One time only Three visits (Day 0, 2 Weeks, 6 Weeks) Maintenance infusion every _____ weeks until _______ (STOP DATE) Vital Signs: Prior to infusion, at every rate increase, and completion Notify Physician if: Systolic BP less than 90 mmHg or greater than 160 mmHg and/or Pulse less than 60/minute or greater than 120/minute and/or Temperature greater than 38.3 C (101 F) For reactions to inFLIXimab STOP INFUSION and initiate Anaphylactic Reaction Med-Induced Physician Orders – (Form #83EANAPX) Supportive Medications: acetaminophen (Tylenol) 650 mg PO Before inFLIXimab dexamethasone (Decadron) 10 mg or 20 mg IVPB or PO Before inFLIXimab diphenhydrAMINE (Benadryl) 25 mg or 50 mg IVPB or PO Before inFLIXimab Other Medications: __________________________________________________________ ___________________________________________________________________________ IV Line Patency Maintenance: NS IV 250 mL at 30 mL/hr during infusion Flush
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2017/0172932 A1 Peyman (43) Pub
    US 20170172932A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0172932 A1 Peyman (43) Pub. Date: Jun. 22, 2017 (54) EARLY CANCER DETECTION AND A 6LX 39/395 (2006.01) ENHANCED IMMUNOTHERAPY A61R 4I/00 (2006.01) (52) U.S. Cl. (71) Applicant: Gholam A. Peyman, Sun City, AZ CPC .......... A61K 9/50 (2013.01); A61K 39/39558 (US) (2013.01); A61K 4I/0052 (2013.01); A61 K 48/00 (2013.01); A61K 35/17 (2013.01); A61 K (72) Inventor: sham A. Peyman, Sun City, AZ 35/15 (2013.01); A61K 2035/124 (2013.01) (21) Appl. No.: 15/143,981 (57) ABSTRACT (22) Filed: May 2, 2016 A method of therapy for a tumor or other pathology by administering a combination of thermotherapy and immu Related U.S. Application Data notherapy optionally combined with gene delivery. The combination therapy beneficially treats the tumor and pre (63) Continuation-in-part of application No. 14/976,321, vents tumor recurrence, either locally or at a different site, by filed on Dec. 21, 2015. boosting the patient’s immune response both at the time or original therapy and/or for later therapy. With respect to Publication Classification gene delivery, the inventive method may be used in cancer (51) Int. Cl. therapy, but is not limited to such use; it will be appreciated A 6LX 9/50 (2006.01) that the inventive method may be used for gene delivery in A6 IK 35/5 (2006.01) general. The controlled and precise application of thermal A6 IK 4.8/00 (2006.01) energy enhances gene transfer to any cell, whether the cell A 6LX 35/7 (2006.01) is a neoplastic cell, a pre-neoplastic cell, or a normal cell.
    [Show full text]
  • Novel Therapies for Eosinophilic Disorders
    Novel Therapies for Eosinophilic Disorders Bruce S. Bochner, MD KEYWORDS Eosinophil Therapies Antibodies Targets Pharmacology Biomarkers KEY POINTS A sizable unmet need exists for new, safe, selective, and effective treatments for eosinophil-associated diseases, such as hypereosinophilic syndrome, eosinophilic gastrointestinal disorders, nasal polyposis, and severe asthma. An improved panel of biomarkers to help guide diagnosis, treatment, and assessment of disease activity is also needed. An impressive array of novel therapeutic agents, including small molecules and biologics, that directly or indirectly target eosinophils and eosinophilic inflammation are undergoing controlled clinical trials, with many already showing promising results. A large list of additional eosinophil-related potential therapeutic targets remains to be pursued, including cell surface structures, soluble proteins that influence eosinophil biology, and eosinophil-derived mediators that have the potential to contribute adversely to disease pathophysiology. INTRODUCTION Eosinophilic disorders, also referred to as eosinophil-associated diseases, consist of a range of infrequent conditions affecting virtually any body compartment and organ.1 The most commonly affected areas include the bone marrow, blood, mucosal sur- faces, and skin, often with immense disease- and treatment-related morbidity, Disclosure Statement: Dr Bochner’s research efforts are supported by grants AI072265, AI097073 and HL107151 from the National Institutes of Health. He has current or recent consul- ting or scientific advisory board arrangements with, or has received honoraria from, Sanofi-A- ventis, Pfizer, Svelte Medical Systems, Biogen Idec, TEVA, and Allakos, Inc. and owns stock in Allakos, Inc. and Glycomimetics, Inc. He receives publication-related royalty payments from Elsevier and UpToDate and is a coinventor on existing and pending Siglec-8-related patents and, thus, may be entitled to a share of future royalties received by Johns Hopkins University on the potential sales of such products.
    [Show full text]