Mechanistic Quantitative Pharmacology Strategies for the Early Clinical Development of Bispecific Antibodies in Oncology

Summary of a workshop on preclinical and translational safety assessment of CD3 bispecifics

(2020) Cris Kamperschroer et al.   Journal of Immunotoxicology

Efficient tumor killing and minimal cytokine release with novel T-cell agonist bispecific antibodies

(2019) Nathan D. Trinklein et al.   mAbs

Bispecific Antibodies in the Treatment of Hematologic Malignancies

(2019) Johannes Duell et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

A Translational Quantitative Systems Pharmacology Model for CD3 Bispecific Molecules: Application to Quantify T Cell-Mediated Tumor Cell Killing by P-Cadherin LP DART®

(2019) Alison Betts et al.   AAPS Journal

Tumor-localized costimulatory T cell engagement by the 4-1BB/HER2 bispecific antibody-Anticalin fusion PRS-343

(2019) Marlon J Hinner et al.   CLINICAL CANCER RESEARCH

A review of bispecific antibodies and antibody constructs in oncology and clinical challenges

(2019) Frans V. Suurs et al.   PHARMACOLOGY & THERAPEUTICS

A Modeling Framework to Characterize Cytokine Release upon T‐Cell–Engaging Bispecific Antibody Treatment: Methodology and Opportunities

(2019) Xiaoying Chen et al.   CTS-Clinical and Translational Science

Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology

(2019) Karen A. Autio et al.   CLINICAL CANCER RESEARCH

Integrated Pharmacokinetic/Pharmacodynamic Model of a Bispecific CD3xCD123 DART Molecule in Nonhuman Primates: Evaluation of Activity and Impact of Immunogenicity

(2018) Olivia Campagne et al.   CLINICAL CANCER RESEARCH

The Role of Quantitative Systems Pharmacology in the Design of First-in-Human Trials

(2018) Piet H. van der Graaf et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Development of a Target cell-Biologics-Effector cell (TBE) complex-based cell killing model to characterize target cell depletion by T cell redirecting bispecific agents

(2018) Xiling Jiang et al.   mAbs

Linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: A comparison between human, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling approach

(2018) Alison Betts et al.   mAbs

Relative Target Affinities of T-Cell–Dependent Bispecific Antibodies Determine Biodistribution in a Solid Tumor Mouse Model

(2018) Danielle Mandikian et al.   MOLECULAR CANCER THERAPEUTICS

Combining expression of GPC3 in tumors and CD16 on NK cells from peripheral blood to identify patients responding to codrituzumab

(2018) Gong Chen et al.   Oncotarget

Antigen-Presenting Cell-Intrinsic PD-1 Neutralizes PD-L1 in cis to Attenuate PD-1 Signaling in T Cells

(2018) Yunlong Zhao et al.   Cell Reports

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

Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies

(2018) Bushra Husain et al.   BIODRUGS

Dual Targeting of Innate and Adaptive Checkpoints on Tumor Cells Limits Immune Evasion

(2018) Xiaojuan Liu et al.   Cell Reports

Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3

(2018) Dionysos Slaga et al.   Science Translational Medicine

Clinical Pharmacology Considerations for the Development of Immune Checkpoint Inhibitors

(2017) Jennifer Sheng et al.   JOURNAL OF CLINICAL PHARMACOLOGY

The making of bispecific antibodies

(2017) Ulrich Brinkmann et al.   mAbs

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

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

Enhanced tumor-targeting selectivity by modulating bispecific antibody binding affinity and format valence

(2017) Yariv Mazor et al.   Scientific Reports

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

(2017) Stephan Kruger et al.   OncoImmunology

Determination of Cellular Processing Rates for a Trastuzumab-Maytansinoid Antibody-Drug Conjugate (ADC) Highlights Key Parameters for ADC Design

(2016) Katie F. Maass et al.   AAPS Journal

An anti-CD3/anti–CLL-1 bispecific antibody for the treatment of acute myeloid leukemia

(2016) Steven R. Leong et al.   BLOOD

Abstract 3217: MGD013, a bispecific PD-1 x LAG-3 Dual-Affinity Re-Targeting (DART®) protein with T-cell immunomodulatory activity for cancer treatment

(2016) Ross LaMotte-Mohs et al.   CANCER RESEARCH

Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody

(2016) Neil H. Segal et al.   CLINICAL CANCER RESEARCH

A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

(2016) M. Bacac et al.   CLINICAL CANCER RESEARCH

Mechanistic Projection of First-in-Human Dose for Bispecific Immunomodulatory P-Cadherin LP-DART: An Integrated PK/PD Modeling Approach

(2016) X Chen et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients

(2016) Michael Ghermezi et al.   HAEMATOLOGICA

Application of a MABEL Approach for a T-Cell-Bispecific Monoclonal Antibody

(2016) Sherri Dudal et al.   JOURNAL OF IMMUNOTHERAPY

Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR -mutated non-small cell lung cancer treated with erlotinib

(2016) Steffen Filskov Sorensen et al.   LUNG CANCER

The application of mathematical modelling to the design of bispecific monoclonal antibodies

(2016) Tamara J. van Steeg et al.   mAbs

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose

(2016) Melissa Lever et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients

(2016) Michael Ghermezi et al.   HAEMATOLOGICA

Impact of Shed/Soluble targets on the PK/PD of approved therapeutic monoclonal antibodies

(2016) Divya Samineni et al.   Expert Review of Clinical Pharmacology

A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma

(2015) A. Rothe et al.   BLOOD

FDA Approval: Blinatumomab

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

The Preclinical Profile of the Duocarmycin-Based HER2-Targeting ADC SYD985 Predicts for Clinical Benefit in Low HER2-Expressing Breast Cancers

(2015) M. M. C. van der Lee et al.   MOLECULAR CANCER THERAPEUTICS

Anti-CD20/CD3 T cell–dependent bispecific antibody for the treatment of B cell malignancies

(2015) Liping L. Sun et al.   Science Translational Medicine

Current concepts in the diagnosis and management of cytokine release syndrome

(2014) D. W. Lee et al.   BLOOD

Preclinical Characterization of AMG 330, a CD3/CD33-Bispecific T-Cell-Engaging Antibody with Potential for Treatment of Acute Myelogenous Leukemia

(2014) M. Friedrich et al.   MOLECULAR CANCER THERAPEUTICS

Cancer heterogeneity: implications for targeted therapeutics

(2013) R Fisher et al.   BRITISH JOURNAL OF CANCER

Immunogenicity of Murine Solid Tumor Models as a Defining Feature of In Vivo Behavior and Response to Immunotherapy

(2013) Melissa G. Lechner et al.   JOURNAL OF IMMUNOTHERAPY

A Comprehensive Mathematical Model for Three-Body Binding Equilibria

(2013) Eugene F. Douglass et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Understanding the role of cross-arm binding efficiency in the activity of monoclonal and multispecific therapeutic antibodies

(2013) Brian D. Harms et al.   METHODS

Recombinant antibody mixtures: Production strategies and cost considerations

(2012) Søren K. Rasmussen et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival

(2012) Eric Sanchez et al.   BRITISH JOURNAL OF HAEMATOLOGY

Dual targeting strategies with bispecific antibodies

(2012) Roland Kontermann   mAbs

Blinatumomab: A historical perspective

(2012) Dirk Nagorsen et al.   PHARMACOLOGY & THERAPEUTICS

Fluorescent reporters of thrombin, heparin cofactor II, and heparin binding in a ternary complex

(2011) Ingrid M. Verhamme   ANALYTICAL BIOCHEMISTRY

Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape

(2011) S.-R. Woo et al.   CANCER RESEARCH

FDA guidance on co-developing investigational drugs

(2011)   NATURE REVIEWS DRUG DISCOVERY

T cell-engaging BiTE antibodies specific for EGFR potently eliminate KRAS- and BRAF-mutated colorectal cancer cells

(2010) Ralf Lutterbuese et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Affinity and Avidity in Antibody-Based Tumor Targeting

(2009) Stephen I. Rudnick et al.   CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS

Serum HER-2/neuand relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer

(2008) Suhail M. Ali et al.   CANCER