A Brief Introduction of Antibody Drug Conjugate Antibody-Drug Conjugates (ADCs) are monoclonal antibodies (mAbs) attached to biologically active drugs (cytotoxic payload) by chemical linkers with labile bonds.

1. Antibody-Drug Conjugates
(ADCs) are monoclonal
antibodies (mAbs) attached
to biologically active drugs
(cytotoxic payloads) by
chemical linkers with labile
bonds.
Structure of antibody-drug conjugate (ADC)1
Mechanism of action of ADC2
To date, four ADCs have
received market approval.
Gemtuzumab ozogamicin
for treatment of acute
myelogenous leukemia,
Brentuximab vedotin for
treatment of relapsed or
refractory Hodgkin lym-
phoma (HL) and systemic
anaplastic large cell
lymphoma (ALCL), Trastu-
zumab emtansine for
tratment of human epider-
mal growth factor receptor
2 (HER2)-positive metastat-
ic breast cancer (mBC), and
Inotuzumab ozogamicin for
treatment of relapsed or
refractory CD22-positive
B-cell precursor acute
lymphoblastic leukemia
(ALL).
Products
Customized ADCs
DrugLnk products
Anti-Ab ADCs
Anti-drug Abs
ANTIBODY-DRUG CONJUGATE
Integrated
Solutions for ADC
Development
Provided by
Creative Biolabs
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Services
ADC Antibody Screening
Antibody-based Probes
DrugLnk™ Custom Synthesis
Antibody Design and Conjugation
ADC in vivo/in vitro Analysis & Manufacturing
Monoclonal
antibody
·Antibody properties
·Internalization
·Receptor-mediated
endocytosis
Cytotoxic payload
·Microtuble inhibitors
-Auristatins
-Maytansines
·DNA synthesis inhibitors
-Calicheamicm
-Doxorubicin
-Duocarmycine
-Pyrrolobenzodiazepine
·Topoisomerase inhibitors
-Quinoline alkaloids
Approved ADC Products for marketing3
Linker
·Cleavable
-Acid-labile
-Protease cleavable
-Disulphide linkage
·Non-cleavable
-Thioether
-Maleimidocaproyl
Name
Gemtuzumab
ozogamicin
Brentuximab
vedotin
Trastuzumab
emtansine
Inotuzumab
ozogamicin
Mylotarg
Adcetris
Kadcyla
Besponsa
Acute myelogenous leukemia
Relapsed or refractory HL and
systemic ALCL
HER2-positive mBC
Relapsed or refractory CD22-
positive B-cell precursor ALL
Wyeth
Pharms Inc.
Seattle
Genetics
Genentech
Wyeth
Pharms Inc.
May 11, 2000
(withdraw 2010)
August 19, 2011
February 22, 2013
August 17, 2017
Trade name Therapeutic area Company First approval date
Antibodies track these
proteins down in the body
and attach themselves to
the surface of cancer cells.
The biochemical reaction
between the antibody and
the target protein (antigen)
triggers a signal in the
tumor cell, which then
absorbs or internalizes the
antibody together with the
cytotoxin. After the ADC is
internalized, the cytotoxic
drug is released and kills
the cancer cell. By combin-
ing the targeting capabili-
ties of monoclonal antibod-
ies with the cancer-killing
ability of cytotoxic drugs,
antibody-drug conjugates
allow for discrimination
between healthy and
diseased tissue.
Route 1
Inhibite DNA synthesis
Route 2
Inhibite microtubles
Route 3
Inhibite topoisomerase
Internalization
Binding
Degradation
Release
Endosome
Lysosome
Nucleus
Microtubules
Route 2
Route 1
Tumor cell
Route
3
ADC