Multispecific drugs herald a new era of biopharmaceutical innovation

Harnessing the Power of Proteolysis for Targeted Protein Inactivation

(2020) Rati Verma et al.   MOLECULAR CELL

Small-molecule targeted recruitment of a nuclease to cleave an oncogenic RNA in a mouse model of metastatic cancer

(2020) Matthew G. Costales et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Treating Disease at the RNA Level with Oligonucleotides

(2019) Arthur A. Levin   NEW ENGLAND JOURNAL OF MEDICINE

Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors

(2019) Gaurav Nayyar et al.   Frontiers in Oncology

Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager

(2019) Jana de Sostoa et al.   Journal for ImmunoTherapy of Cancer

Antibody–Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity

(2019) Dario Neri   Cancer Immunology Research

Clinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemia

(2019) Juanjuan Zhao et al.   Journal of Hematology & Oncology

Logic-Gated ROR1 Chimeric Antigen Receptor Expression Rescues T Cell-Mediated Toxicity to Normal Tissues and Enables Selective Tumor Targeting

(2019) Shivani Srivastava et al.   CANCER CELL

Taking a "BiTE out of ALL" - Blinautmomab approval for MRD positive ALL

(2019) Emily Curran et al.   BLOOD

Re-Engineering RNA Molecules into Therapeutic Agents

(2019) Martin Egli et al.   ACCOUNTS OF CHEMICAL RESEARCH

Targeting Nuclear Receptors with PROTAC degraders

(2019) John J. Flanagan et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity

(2019) Laurent Gauthier et al.   CELL

Therapeutic Ligands Antagonize Estrogen Receptor Function by Impairing Its Mobility

(2019) Jane Guan et al.   CELL

De novo design of bioactive protein switches

(2019) Robert A. Langan et al.   NATURE

Bispecific antibodies: a mechanistic review of the pipeline

(2019) Aran F. Labrijn et al.   NATURE REVIEWS DRUG DISCOVERY

Multispecific targeting with synthetic ankyrin repeat motif chimeric antigen receptors

(2019) Ashwini Balakrishnan et al.   CLINICAL CANCER RESEARCH

Targeting cardiac fibrosis with engineered T cells

(2019) Haig Aghajanian et al.   NATURE

Chronic inflammation in multiple sclerosis — seeing what was always there

(2019) Paul M. Matthews   Nature Reviews Neurology

CD3 bispecific antibody–induced cytokine release is dispensable for cytotoxic T cell activity

(2019) Ji Li et al.   Science Translational Medicine

Bifunctional Small-Molecule Ligands of K-Ras Induce Its Association with Immunophilin Proteins

(2019) Ziyang Zhang et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Bifunctional chemical probes inducing protein–protein interactions

(2019) Chiara Maniaci et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study

(2019) Sayumi Yamazoe et al.   JOURNAL OF MEDICINAL CHEMISTRY

AUTACs: Cargo-Specific Degraders Using Selective Autophagy

(2019) Daiki Takahashi et al.   MOLECULAR CELL

Bispecific antibodies in haematological malignancies

(2018) Andreas Viardot et al.   CANCER TREATMENT REVIEWS

Antiviral Activity of HIV gp120-Targeting Bispecific T Cell Engager Antibody Constructs

(2018) Johannes Brozy et al.   JOURNAL OF VIROLOGY

Advanced siRNA Designs Further Improve In Vivo Performance of GalNAc-siRNA Conjugates

(2018) Donald J. Foster et al.   MOLECULAR THERAPY

FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell‐Induced Severe or Life‐Threatening Cytokine Release Syndrome

(2018) Robert Q. Le et al.   ONCOLOGIST

Chemically induced proximity in biology and medicine

(2018) Benjamin Z. Stanton et al.   SCIENCE

Extrahepatic Targeting of Oligonucleotides with Receptor-Binding Non-Immunoglobulin Scaffold Proteins

(2018) Johannes Winkler   Nucleic Acid Therapeutics

GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics

(2018) Aaron D. Springer et al.   Nucleic Acid Therapeutics

A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors

(2018) Maxim Kebenko et al.   OncoImmunology

An approved in vitro approach to preclinical safety and efficacy evaluation of engineered T cell receptor anti-CD3 bispecific (ImmTAC) molecules

(2018) Jane Harper et al.   PLoS One

Emicizumab, a humanized bispecific antibody to coagulation factors IXa and X with a factor VIIIa-cofactor activity

(2018) Takehisa Kitazawa et al.   INTERNATIONAL JOURNAL OF HEMATOLOGY

Antibody-drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes

(2018) Meghdad Abdollahpour-Alitappeh et al.   JOURNAL OF CELLULAR PHYSIOLOGY

The chemical evolution of oligonucleotide therapies of clinical utility

(2017) Anastasia Khvorova et al.   NATURE BIOTECHNOLOGY

Selective degradation of splicing factor CAPERα by anticancer sulfonamides

(2017) Taisuke Uehara et al.   Nature Chemical Biology

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd et al.   Nature Chemical Biology

Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems

(2017) Ken Y Chan et al.   NATURE NEUROSCIENCE

Strategies and challenges for the next generation of antibody–drug conjugates

(2017) Alain Beck et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting blood-brain-barrier transcytosis – perspectives for drug delivery

(2017) Imre Mäger et al.   NEUROPHARMACOLOGY

Antibody therapies in CNS diseases

(2017) Per-Ola Freskgård et al.   NEUROPHARMACOLOGY

An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection

(2017) Haleh Saber et al.   REGULATORY TOXICOLOGY AND PHARMACOLOGY

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

(2017) Ting Han et al.   SCIENCE

Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits

(2016) Kole T. Roybal et al.   CELL

Aberrant bispecific antibody pharmacokinetics linked to liver sinusoidal endothelium clearance mechanism in cynomolgus monkeys

(2016) Amita Datta-Mannan et al.   mAbs

The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

(2016) Jeff Sevigny et al.   NATURE

Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

(2016) Darren J. Baker et al.   NATURE

Discovery of Novel Blood-Brain Barrier Targets to Enhance Brain Uptake of Therapeutic Antibodies

(2016) Y. Joy Yu Zuchero et al.   NEURON

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

(2016) C. T. Ellebrecht et al.   SCIENCE

siRNA Conjugates Carrying Sequentially Assembled Trivalent N-Acetylgalactosamine Linked Through Nucleosides Elicit Robust Gene Silencing In Vivo in Hepatocytes

(2015) Shigeo Matsuda et al.   ACS Chemical Biology

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle et al.   ACS Chemical Biology

Targeting Receptor-Mediated Transport for Delivery of Biologics Across the Blood-Brain Barrier

(2015) Jason M. Lajoie et al.   Annual Review of Pharmacology and Toxicology

A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3

(2015) Morten Mau-Sørensen et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

FDA Approval: Blinatumomab

(2015) D. Przepiorka et al.   CLINICAL CANCER RESEARCH

Catalytic in vivo protein knockdown by small-molecule PROTACs

(2015) Daniel P Bondeson et al.   Nature Chemical Biology

SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice

(2015) James Palacino et al.   Nature Chemical Biology

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

Combinatorial Approaches for the Identification of Brain Drug Delivery Targets

(2014) Charles Stutz et al.   CURRENT PHARMACEUTICAL DESIGN

Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing

(2014) Jayaprakash K. Nair et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN

(2013) Anita K. Gandhi et al.   BRITISH JOURNAL OF HAEMATOLOGY

Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria

(2013) Chiaki Ito et al.   MOLECULAR CELL

Identification and Multidimensional Optimization of an Asymmetric Bispecific IgG Antibody Mimicking the Function of Factor VIII Cofactor Activity

(2013) Zenjiro Sampei et al.   PLoS One

Engineered Monoclonal Antibody with Novel Antigen-Sweeping Activity In Vivo

(2013) Tomoyuki Igawa et al.   PLoS One

Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells

(2013) J. Kronke et al.   SCIENCE

The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins

(2013) G. Lu et al.   SCIENCE

Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index

(2013) L. R. Desnoyers et al.   Science Translational Medicine

Small-Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α

(2012) Dennis L. Buckley et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL

(2012) M. S. Topp et al.   BLOOD

Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide

(2012) A Lopez-Girona et al.   LEUKEMIA

Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma

(2012) Yuan Xiao Zhu et al.   LEUKEMIA & LYMPHOMA

Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells

(2012) Christopher C Kloss et al.   NATURE BIOTECHNOLOGY

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

CAT-8015: A Second-Generation Pseudomonas Exotoxin A-Based Immunotherapy Targeting CD22-Expressing Hematologic Malignancies

(2009) R. F. Alderson et al.   CLINICAL CANCER RESEARCH

Structural Basis for the Blockage of IL-2 Signaling by Therapeutic Antibody Basiliximab

(2009) J. Du et al.   JOURNAL OF IMMUNOLOGY

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

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

The Anchor-Away Technique: Rapid, Conditional Establishment of Yeast Mutant Phenotypes

(2008) Hirohito Haruki et al.   MOLECULAR CELL

Tumor Regression in Cancer Patients by Very Low Doses of a T Cell-Engaging Antibody

(2008) R. Bargou et al.   SCIENCE