antibody-drug conjugate - creative biolabs · 2021. 1. 6. · antibody-drug conjugates (adcs) are...

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 ADC 2 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 lymphoma (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 WHAT WE DO: © 2020 Creative-Biolabs All Rights Reserved Email: [email protected] Tel: 1-631-357-2254 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 marketing 3 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 antibodies 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

Upload: others

Post on 23-Jan-2021

13 views

Category:

Documents

0 download

Report

Download

Embed Size (px):

TRANSCRIPT

Page 1: Antibody-Drug Conjugate - Creative Biolabs · 2021. 1. 6. · Antibody-Drug Conjugates (ADCs) are monoclonal antibodies (mAbs) attached to biologically active drugs (cytotoxic payloads)

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 acutelymphoblastic leukemia(ALL).

Products Customized ADCs DrugLnk products Anti-Ab ADCs Anti-drug Abs

ANTIBODY-DRUG CONJUGATE

IntegratedSolutions for ADCDevelopmentProvided byCreative Biolabs

WHAT WE DO:

Services ADC Antibody Screening Antibody-based Probes DrugLnk™ Custom Synthesis Antibody Design and Conjugation ADC in vivo/in vitro Analysis & Manufacturing

Monoclonalantibody

·Antibody properties·Internalization·Receptor-mediatedendocytosis

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

Gemtuzumabozogamicin

Brentuximabvedotin

Trastuzumabemtansine

Inotuzumabozogamicin

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 1Inhibite DNA synthesis

Route 2Inhibite microtubles

Route 3Inhibite topoisomerase

Internalization

Binding

Degradation

Release

Endosome Lysosome

Nucleus

MicrotubulesRoute 2

Route 1Tumor cell

Route