Challenges and approaches for the development of safer immunomodulatory biologics

Complement Activation Plays a Key Role in Antibody-Induced Infusion Toxicity in Monkeys and Rats

(2014) T. Tawara et al.   JOURNAL OF IMMUNOLOGY

Antagonizing the  4 1 Integrin, but Not  4 7, Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

(2013) K. G. Haanstra et al.   JOURNAL OF IMMUNOLOGY

Immunogenicity to Therapeutic Proteins: Impact on PK/PD and Efficacy

(2012) Narendra Chirmule et al.   AAPS Journal

Immunogenicity to Biologics: Mechanisms, Prediction and Reduction

(2012) Swaminathan Sethu et al.   ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS

Rates of malignancy associated with juvenile idiopathic arthritis and its treatment

(2012) Timothy Beukelman et al.   ARTHRITIS AND RHEUMATISM

Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients

(2012) G. Salles et al.   BLOOD

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation

(2012) A. K. Gopal et al.   BLOOD

Belatacept: a new biological agent for maintenance immunosuppression in kidney transplantation

(2012) Swati Arora et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Safety of rituximab in rheumatoid arthritis: A long-term prospective single-center study of gammaglobulin concentrations and infections

(2012) Anne Isvy et al.   JOINT BONE SPINE

Highly Aggregated Antibody Therapeutics Can Enhance thein VitroInnate and Late-stage T-cell Immune Responses

(2012) Marisa K. Joubert et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Different Adaptations of IgG Effector Function in Human and Nonhuman Primates and Implications for Therapeutic Antibody Treatment

(2012) M. Warncke et al.   JOURNAL OF IMMUNOLOGY

Summary of roundtable discussion meeting: Non-human primates to assess risk for EBV-related lymphomas in humans

(2012) Thomas Kawabata et al.   Journal of Immunotoxicology

A predictive biomimetic model of cytokine release induced by TGN1412 and other therapeutic monoclonal antibodies

(2012) Vipra Dhir et al.   Journal of Immunotoxicology

Relationship Between Potential Aggregation-Prone Regions and HLA-DR-Binding T-Cell Immune Epitopes: Implications for Rational Design of Novel and Follow-on Therapeutic Antibodies

(2012) Sandeep Kumar et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

Short-term Risk of Total Malignancy and Nonmelanoma Skin Cancers with Certolizumab and Golimumab in Patients with Rheumatoid Arthritis: Metaanalysis of Randomized Controlled Trials

(2012) P. LE BLAY et al.   JOURNAL OF RHEUMATOLOGY

Pharmacokinetics and tolerability of human mouse chimeric anti-CD22 monoclonal antibody in Chinese patients with CD22-positive non-Hodgkin lymphoma

(2012) Su Li et al.   mAbs

Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab

(2012) Per Soelberg Sørensen et al.   Multiple Sclerosis Journal

Ustekinumab shows promise in the treatment of refractory Crohn's disease

(2012) Katrina Ray   Nature Reviews Gastroenterology & Hepatology

Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

(2012) Gary Bloomgren et al.   NEW ENGLAND JOURNAL OF MEDICINE

Blinatumomab: A historical perspective

(2012) Dirk Nagorsen et al.   PHARMACOLOGY & THERAPEUTICS

The Yin and Yang of Immunomodulatory Biologics: Assessing the Delicate Balance between Benefit and Risk

(2012) Dimitry M. Danilenko et al.   TOXICOLOGIC PATHOLOGY

Concordance of preclinical and clinical pharmacology and toxicology of monoclonal antibodies and fusion proteins: soluble targets

(2011) Pauline L Martin et al.   BRITISH JOURNAL OF PHARMACOLOGY

Concordance of preclinical and clinical pharmacology and toxicology of therapeutic monoclonal antibodies and fusion proteins: cell surface targets

(2011) Peter J Bugelski et al.   BRITISH JOURNAL OF PHARMACOLOGY

Use of Biologics in Rheumatoid Arthritis: Current and Emerging Paradigms of Care

(2011) Jeffrey R. Curtis et al.   CLINICAL THERAPEUTICS

Autoimmune hepatitis induced by adalimumab with successful switch to abatacept

(2011) A. Grasland et al.   EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY

Diversity of MHC class I haplotypes in cynomolgus macaques

(2011) Yusuke Saito et al.   IMMUNOGENETICS

Vedolizumab for the Treatment of Active Ulcerative Colitis: A Randomized Controlled Phase 2 Dose-ranging Study

(2011) Asit Parikh et al.   INFLAMMATORY BOWEL DISEASES

Development of a human whole blood assay for prediction of cytokine release similar to anti-CD28 superagonists using multiplex cytokine and hierarchical cluster analysis

(2011) Mindi R. Walker et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up

(2011) Geertje M. Bartelds   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Reactivation of occult hepatitis B virus infection, following treatment of refractory rheumatoid arthritis with abatacept

(2011) Georgios Germanidis et al.   JOURNAL OF HEPATOLOGY

Recombinant and Natural Human Interferons: Analysis of the Incidence and Clinical Impact of Neutralizing Antibodies

(2011) David R. Strayer et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

Aggregation in Protein-Based Biotherapeutics: Computational Studies and Tools to Identify Aggregation-Prone Regions

(2011) Neeraj J. Agrawal et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: A systematic review and meta-analysis of randomized controlled trials

(2011) Erica D. Dommasch et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

TNF-α Antagonist Use and Risk of Hospitalization for Infection in a National Cohort of Veterans With Rheumatoid Arthritis

(2011) Michael A. Lane et al.   MEDICINE

Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab

(2011) Per Soelberg Sørensen et al.   Multiple Sclerosis Journal

Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

(2011) Guangmei Yan et al.   NATURE BIOTECHNOLOGY

How were new medicines discovered?

(2011) David C. Swinney et al.   NATURE REVIEWS DRUG DISCOVERY

Susceptibility of patients with rheumatic diseases to B-cell non-Hodgkin lymphoma

(2011) Catarina Dias et al.   Nature Reviews Rheumatology

Lebrikizumab Treatment in Adults with Asthma

(2011) Jonathan Corren et al.   NEW ENGLAND JOURNAL OF MEDICINE

Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?

(2011) N. B. Watts et al.   OSTEOPOROSIS INTERNATIONAL

Coupling of Aggregation and Immunogenicity in Biotherapeutics: T- and B-Cell Immune Epitopes May Contain Aggregation-Prone Regions

(2011) Sandeep Kumar et al.   PHARMACEUTICAL RESEARCH

Immunogenicity of Therapeutic Proteins: The Use of Animal Models

(2011) Vera Brinks et al.   PHARMACEUTICAL RESEARCH

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

(2011) Geertje M Bartelds et al.   ARTHRITIS RESEARCH & THERAPY

In vitrocytokine release assays: reducing the risk of adverse events in man

(2011) Christopher M Kirton et al.   Bioanalysis

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study

(2010) S. J. O'Day et al.   ANNALS OF ONCOLOGY

A case of progressive multifocal leukoencephalopathy in a patient treated with infliximab

(2010) Deepak Kumar et al.   ARTHRITIS AND RHEUMATISM

PEGylation of therapeutic proteins

(2010) Simona Jevševar et al.   Biotechnology Journal

Multiple signaling pathways induced by hexavalent, monospecific, anti-CD20 and hexavalent, bispecific, anti-CD20/CD22 humanized antibodies correlate with enhanced toxicity to B-cell lymphomas and leukemias

(2010) P. Gupta et al.   BLOOD

Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity

(2010) E. Mossner et al.   BLOOD

Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patients

(2010) Peter Ruf et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells

(2010) D Eastwood et al.   BRITISH JOURNAL OF PHARMACOLOGY

Immunity, Inflammation, and Cancer

(2010) Sergei I. Grivennikov et al.   CELL

Interferon beta inhibits the Th17 cell-mediated autoimmune response in patients with relapsing–remitting multiple sclerosis

(2010) Xin Zhang et al.   CLINICAL NEUROLOGY AND NEUROSURGERY

Subset analysis of patients experiencing clinical events of a potentially immunogenic nature in the pivotal clinical trials of tocilizumab for rheumatoid arthritis: Evaluation of an antidrug antibody ELISA using clinical adverse event-driven immunogenicity testing

(2010) Kay Stubenrauch et al.   CLINICAL THERAPEUTICS

Anti-TNF Antibody Therapy for Inflammatory Bowel Disease During Pregnancy: A Clinical Review

(2010) Marwa Mourabet et al.   CURRENT DRUG TARGETS

In vitro cytokine release assays for predicting cytokine release syndrome: The current state-of-the-science. Report of a European Medicines Agency Workshop

(2010) Jean-Marc Vidal et al.   CYTOKINE

Monoclonal antibodies and fusion proteins and their complications: Targeting B cells in autoimmune diseases

(2010) Susan Lee et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Legionella pneumophila pneumonia in a pregnant woman treated with anti-TNF-α antibodies for Crohn's disease: A case report

(2010) G. Epping et al.   Journal of Crohns & Colitis

A Novel Strategy To Reduce the Immunogenicity of Biological Therapies

(2010) J. Somerfield et al.   JOURNAL OF IMMUNOLOGY

On the Role of Aggregates in the Immunogenicity of Recombinant Human Interferon Beta in Patients with Multiple Sclerosis

(2010) Miranda M.C. van Beers et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

Impact of Product-Related Factors on Immunogenicity of Biotherapeutics

(2010) Satish Kumar Singh   JOURNAL OF PHARMACEUTICAL SCIENCES

Preclinical development of monoclonal antibodies

(2010) Kathryn Chapman et al.   mAbs

Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies

(2010) Frank R. Brennan et al.   mAbs

Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins

(2010) Darius Ghaderi et al.   NATURE BIOTECHNOLOGY

The safety and side effects of monoclonal antibodies

(2010) Trevor T. Hansel et al.   NATURE REVIEWS DRUG DISCOVERY

Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis

(2010) H. Huang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Incidences and Range of Spontaneous Findings in Control Cynomolgus Monkeys (Macaca fascicularis) Used in Toxicity Studies

(2010) Ronnie Chamanza et al.   TOXICOLOGIC PATHOLOGY

An Integrated Safety Profile Analysis of Belatacept in Kidney Transplant Recipients

(2010) Josep Grinyó et al.   TRANSPLANTATION

Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice

(2009) Y. ZABANA et al.   ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry

(2009) J D Greenberg et al.   ANNALS OF THE RHEUMATIC DISEASES

Anti-adalimumab antibodies in rheumatoid arthritis patients are associated with interleukin-10 gene polymorphisms

(2009) G. M. Bartelds et al.   ARTHRITIS AND RHEUMATISM

Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics

(2009) Anne S. De Groot et al.   CLINICAL IMMUNOLOGY

Anaphylaxis After Administration of Ibritumomab Tiuxetan for Follicular Non-Hodgkin Lymphoma

(2009) Rachel Jankowitz et al.   CLINICAL NUCLEAR MEDICINE

Safety Assessment and Dose Selection for First-in-Human Clinical Trials With Immunomodulatory Monoclonal Antibodies

(2009) PY Muller et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies

(2009) Patrick Y Muller et al.   CURRENT OPINION IN BIOTECHNOLOGY

Translational strategies for development of monoclonal antibodies from discovery to the clinic

(2009) Mohammad A. Tabrizi et al.   DRUG DISCOVERY TODAY

Alternative Strategies for Toxicity Testing of Species-Specific Biopharmaceuticals

(2009) Jeanine L. Bussiere et al.   INTERNATIONAL JOURNAL OF TOXICOLOGY

Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations

(2009) Raymond G. Slavin et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Structural and Functional Analysis of a C3b-specific Antibody That Selectively Inhibits the Alternative Pathway of Complement

(2009) Kenneth J. Katschke et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy

(2009) David L Kendler et al.   JOURNAL OF BONE AND MINERAL RESEARCH

Hybrid transgenic immune tolerant mouse model for assessing the breaking of B cell tolerance by human interferon beta

(2009) Miranda M.C. van Beers et al.   JOURNAL OF IMMUNOLOGICAL METHODS

Opportunistic infections in non-human primates exposed to immunomodulatory biotherapeutics: considerations and case examples

(2009) David L. Hutto   Journal of Immunotoxicology

Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project

(2009) Kenneth R Carson et al.   LANCET ONCOLOGY

Glycosylation as a strategy to improve antibody-based therapeutics

(2009) Roy Jefferis   NATURE REVIEWS DRUG DISCOVERY

Immunogenicity of biologically-derived therapeutics: Assessment and interpretation of nonclinical safety studies

(2009) Rafael Ponce et al.   REGULATORY TOXICOLOGY AND PHARMACOLOGY

The EMEA Guideline on First-in-Human Clinical Trials and Its Impact on Pharmaceutical Development

(2009) Mark N. Milton et al.   TOXICOLOGIC PATHOLOGY

Structural characterization of a human Fc fragment engineered for lack of effector functions

(2008) Vaheh Oganesyan et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic review and individual patient data meta-analysis of randomised controlled trials

(2008) T Bongartz et al.   ANNALS OF THE RHEUMATIC DISEASES

Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: A twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial

(2008) Stanley B. Cohen et al.   ARTHRITIS AND RHEUMATISM

Serious infections during anti-TNFα treatment in rheumatoid arthritis patients

(2008) Ennio Giulio Favalli et al.   AUTOIMMUNITY REVIEWS

Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes"

(2008) A. S. De Groot et al.   BLOOD

Pharmacokinetic and pharmacodynamic properties of TRU-015, a CD20-directed small modular immunopharmaceutical protein therapeutic, in patients with rheumatoid arthritis: A phase I, open-label, dose-escalation clinical study

(2008) Daniel J. Burge et al.   CLINICAL THERAPEUTICS

The emergence of progressive multifocal leukoencephalopathy (PML) in rheumatic diseases

(2008) Eric J. Boren et al.   JOURNAL OF AUTOIMMUNITY

A multicenter, open‐label study of repeat courses of intramuscular alefacept in combination with other psoriasis therapies in patients with chronic plaque psoriasis

(2008) Gerald G. Krueger et al.   JOURNAL OF DERMATOLOGICAL TREATMENT

Adverse Consequences of Immunostimulation

(2008) Rafael Ponce   Journal of Immunotoxicology

Predicting linear B‐cell epitopes using string kernels

(2008) Yasser EL‐Manzalawy et al.   JOURNAL OF MOLECULAR RECOGNITION

Alemtuzumab vs. Interferon Beta-1a in Early Multiple Sclerosis

(2008)   NEW ENGLAND JOURNAL OF MEDICINE

A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene

(2007) Marie King et al.   CLINICAL IMMUNOLOGY

Protein therapeutics: a summary and pharmacological classification

(2007) Benjamin Leader et al.   NATURE REVIEWS DRUG DISCOVERY