Antibody-Drug Conjugates as Cancer Therapeutics: Past, Present, and Future

Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study

(2017) Charles M Rudin et al.   LANCET ONCOLOGY

Evolution of Antibody-Drug Conjugate Tumor Disposition Model to Predict Preclinical Tumor Pharmacokinetics of Trastuzumab-Emtansine (T-DM1)

(2016) Aman P. Singh et al.   AAPS Journal

Multiscale Modeling of Antibody-Drug Conjugates: Connecting Tissue and Cellular Distribution to Whole Animal Pharmacokinetics and Potential Implications for Efficacy

(2016) Cornelius Cilliers et al.   AAPS Journal

SNAP-Tag Technology: A Useful Tool To Determine Affinity Constants and Other Functional Parameters of Novel Antibody Fragments

(2016) Judith Niesen et al.   BIOCONJUGATE CHEMISTRY

Antibody-drug conjugates—an emerging class of cancer treatment

(2016) Nikolaos Diamantis et al.   BRITISH JOURNAL OF CANCER

The efficient elimination of solid tumor cells by EGFR-specific and HER2-specific scFv-SNAP fusion proteins conjugated to benzylguanine-modified auristatin F

(2016) Mira Woitok et al.   CANCER LETTERS

Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer

(2016) J. Baselga et al.   CLINICAL CANCER RESEARCH

New developments for antibody-drug conjugate-based therapeutic approaches

(2016) Bart ECG de Goeij et al.   CURRENT OPINION IN IMMUNOLOGY

Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T-DM1)vs. treatment of physician's choice in previously treated HER2-positive advanced breast cancer

(2016) Sung-Bae Kim et al.   INTERNATIONAL JOURNAL OF CANCER

Current Status: Site-Specific Antibody Drug Conjugates

(2016) Dominik Schumacher et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Model-based pharmacokinetic analysis of elotuzumab in patients with relapsed/refractory multiple myeloma

(2016) Leonid Gibiansky et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

(2016) Ruchi Bansal et al.   MEDIATORS OF INFLAMMATION

Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins

(2016) Prince Awuah et al.   MOLECULAR CANCER THERAPEUTICS

Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection

(2015) S. Sadekar et al.   AAPS Journal

Antibody Drug Conjugates: Nonclinical Safety Considerations

(2015) Mary Jane Masson Hinrichs et al.   AAPS Journal

Versatile and Efficient Site-Specific Protein Functionalization by Tubulin Tyrosine Ligase

(2015) Dominik Schumacher et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics

(2015) Eunhee G. Kim et al.   Biomolecules & Therapeutics

Challenges and advances in the assessment of the disposition of antibody-drug conjugates

(2015) Amrita V. Kamath et al.   BIOPHARMACEUTICS & DRUG DISPOSITION

Antibody-drug conjugates as novel anti-cancer chemotherapeutics

(2015) C. Peters et al.   BIOSCIENCE REPORTS

A Polymer-Based Antibody-Vinca Drug Conjugate Platform: Characterization and Preclinical Efficacy

(2015) A. V. Yurkovetskiy et al.   CANCER RESEARCH

EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB–Expressing Breast Cancer

(2015) Denise A. Yardley et al.   JOURNAL OF CLINICAL ONCOLOGY

Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial

(2015) Craig H Moskowitz et al.   LANCET

Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index

(2015) Robert P Lyon et al.   NATURE BIOTECHNOLOGY

An FDA oncology analysis of antibody-drug conjugates

(2015) Haleh Saber et al.   REGULATORY TOXICOLOGY AND PHARMACOLOGY

Trastuzumab emtansine (T-DM1) renders HER2 + breast cancer highly susceptible to CTLA-4/PD-1 blockade

(2015) Philipp Müller et al.   Science Translational Medicine

A Mechanistic Tumor Penetration Model to Guide Antibody Drug Conjugate Design

(2015) Christina Vasalou et al.   PLoS One

A Priori Prediction of Tumor Payload Concentrations: Preclinical Case Study with an Auristatin-Based Anti-5T4 Antibody-Drug Conjugate

(2014) Dhaval K. Shah et al.   AAPS Journal

Immunogenicity of Antibody Drug Conjugates: Bioanalytical Methods and Monitoring Strategy for a Novel Therapeutic Modality

(2014) M. Benjamin Hock et al.   AAPS Journal

Practical Considerations for the Pharmacokinetic and Immunogenic Assessment of Antibody–Drug Conjugates

(2014) Melody Sauerborn et al.   BIODRUGS

Population pharmacokinetics of trastuzumab emtansine (T-DM1), a HER2-targeted antibody–drug conjugate, in patients with HER2-positive metastatic breast cancer: clinical implications of the effect of covariates

(2014) Dan Lu et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Physiologically Based Pharmacokinetic Modeling as a Tool to Predict Drug Interactions for Antibody-Drug Conjugates

(2014) Yuan Chen et al.   CLINICAL PHARMACOKINETICS

Cancer, Inflammation, and Therapy: Effects on Cytochrome P450–Mediated Drug Metabolism and Implications for Novel Immunotherapeutic Agents

(2014) R Donald Harvey et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in-human Phase 1 studies

(2014) Antoine Deslandes   mAbs

Microtubule-Depolymerizing Agents Used in Antibody-Drug Conjugates Induce Antitumor Immunity by Stimulation of Dendritic Cells

(2014) P. Muller et al.   Cancer Immunology Research

Drug–Drug Interaction Studies: Regulatory Guidance and An Industry Perspective

(2013) Thomayant Prueksaritanont et al.   AAPS Journal

Therapeutic Protein Drug–Drug Interactions: Navigating the Knowledge Gaps–Highlights from the 2012 AAPS NBC Roundtable and IQ Consortium/FDA Workshop

(2013) Jane R. Kenny et al.   AAPS Journal

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies

(2013) T. H. Han et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer

(2013) Dan Lu et al.   CLINICAL PHARMACOKINETICS

Antibody–drug conjugates: current status and future directions

(2013) Heidi L. Perez et al.   DRUG DISCOVERY TODAY

On translation of antibody drug conjugates efficacy from mouse experimental tumors to the clinic: a PK/PD approach

(2013) Nahor Haddish-Berhane et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Site-specific antibody drug conjugates for cancer therapy

(2013) Siler Panowski et al.   mAbs

Bioanalysis of antibody–drug conjugates: American Association of Pharmaceutical Scientists Antibody–Drug Conjugate Working Group position paper

(2013) Boris Gorovits et al.   Bioanalysis

Bioanalytical assay strategies for the development of antibody–drug conjugate biotherapeutics

(2013) Surinder Kaur et al.   Bioanalysis

Compartmental Tissue Distribution of Antibody Therapeutics: Experimental Approaches and Interpretations

(2012) C. Andrew Boswell et al.   AAPS Journal

A population pharmacokinetic/pharmacodynamic model of thrombocytopenia characterizing the effect of trastuzumab emtansine (T-DM1) on platelet counts in patients with HER2-positive metastatic breast cancer

(2012) Brendan C. Bender et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

A Guide to Rational Dosing of Monoclonal Antibodies

(2012) Shuang Bai et al.   CLINICAL PHARMACOKINETICS

Effects of Interleukin 1β (IL-1β) and IL-1β/Interleukin 6 (IL-6) Combinations on Drug Metabolizing Enzymes in Human Hepatocyte Culture

(2012) Leslie J. Dickmann et al.   CURRENT DRUG METABOLISM

Brentuximab Vedotin (SGN-35) in Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma: Results of a Phase II Study

(2012) Barbara Pro et al.   JOURNAL OF CLINICAL ONCOLOGY

Differential Effects of Predosing on Tumor and Tissue Uptake of an 111In-Labeled Anti-TENB2 Antibody-Drug Conjugate

(2012) C. A. Boswell et al.   JOURNAL OF NUCLEAR MEDICINE

Bench to bedside translation of antibody drug conjugates using a multiscale mechanistic PK/PD model: a case study with brentuximab-vedotin

(2012) Dhaval K. Shah et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

The Effect of Different Linkers on Target Cell Catabolism and Pharmacokinetics/Pharmacodynamics of Trastuzumab Maytansinoid Conjugates

(2012) H. K. Erickson et al.   MOLECULAR CANCER THERAPEUTICS

Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer

(2012) Sunil Verma et al.   NEW ENGLAND JOURNAL OF MEDICINE

Anti-Neuropilin-1 (MNRP1685A): Unexpected Pharmacokinetic Differences Across Species, from Preclinical Models to Humans

(2012) Yan Xin et al.   PHARMACEUTICAL RESEARCH

Pharmacokinetic Considerations for Antibody Drug Conjugates

(2012) Kedan Lin et al.   PHARMACEUTICAL RESEARCH

Synthesis of site-specific antibody-drug conjugates using unnatural amino acids

(2012) J. Y. Axup et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mechanisms of Monoclonal Antibody–Drug Interactions

(2011) Honghui Zhou et al.   Annual Review of Pharmacology and Toxicology

Cytotoxic Activity of Immunotoxin SS1P Is Modulated by TACE-Dependent Mesothelin Shedding

(2011) Y. Zhang et al.   CANCER RESEARCH

Trastuzumab Emtansine: A Unique Antibody-Drug Conjugate in Development for Human Epidermal Growth Factor Receptor 2-Positive Cancer

(2011) P. M. LoRusso et al.   CLINICAL CANCER RESEARCH

Clinical Implications of Pathophysiological and Demographic Covariates on the Population Pharmacokinetics of Trastuzumab Emtansine, a HER2-Targeted Antibody-Drug Conjugate, in Patients With HER2-Positive Metastatic Breast Cancer

(2011) Manish Gupta et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer

(2010) Teemu T. Junttila et al.   BREAST CANCER RESEARCH AND TREATMENT

Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies

(2010) Ron J. Keizer et al.   CLINICAL PHARMACOKINETICS

Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer

(2010) Ian E. Krop et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy

(2010) Howard A. Burris et al.   JOURNAL OF CLINICAL ONCOLOGY

Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas

(2010) Anas Younes et al.   NEW ENGLAND JOURNAL OF MEDICINE

A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy

(2009) R. M. Sharkey et al.   BLOOD

Fixed Dosing Versus Body Size-Based Dosing of Monoclonal Antibodies in Adult Clinical Trials

(2009) Diane D. Wang et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Pretargeted Versus Directly Targeted Radioimmunotherapy Combined with Anti-CD20 Antibody Consolidation Therapy of Non-Hodgkin Lymphoma

(2009) R. M. Sharkey et al.   JOURNAL OF NUCLEAR MEDICINE

Dose Escalation Methods in Phase I Cancer Clinical Trials

(2009) Christophe Le Tourneau et al.   JNCI-Journal of the National Cancer Institute

High Shed Antigen Levels within Tumors: An Additional Barrier to Immunoconjugate Therapy

(2008) Y. Zhang et al.   CLINICAL CANCER RESEARCH

Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index

(2008) C. F. McDonagh et al.   MOLECULAR CANCER THERAPEUTICS