John M. Lambert
ImmunoGen, Inc.
CytotoxicityPharmacokineticsImmunotoxinAntigenMolecular biologyCytotoxic T cellAntibodyChemistryConjugateImmunologyIn vivoRicinAntibody-drug conjugateImmunoconjugateMaytansinoidCancer researchMonoclonal antibodyBiochemistryMedicineBiologyPharmacology
Publications 103
#1Xiuxia Sun (ImmunoGen, Inc.)H-Index: 6
#2Jose F. Ponte (ImmunoGen, Inc.)H-Index: 10
Last. John M. LambertH-Index: 52
view all 21 authors...
Antibody–drug conjugates (ADCs) are being actively pursued as a treatment option for cancer following the regulatory approval of brentuximab vedotin (Adcetris) and ado-trastuzumab emtansine (Kadcyla). ADCs consist of a cytotoxic agent conjugated to a targeting antibody through a linker. The two approved ADCs (and most ADCs now in the clinic that use a microtubule disrupting agent as the payload) are heterogeneous conjugates with an average drug-to-antibody ratio (DAR) of 3–4 (potentially ranging...
58 CitationsSource
#1John M. Lambert (ImmunoGen, Inc.)H-Index: 52
#2Charles Q. Morris (ImmunoGen, Inc.)H-Index: 1
Attaching a cytotoxic “payload” to an antibody to form an antibody–drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It wa...
130 CitationsSource
#1John M. Lambert (ImmunoGen, Inc.)H-Index: 52
7 CitationsSource
#1Michael L. Miller (ImmunoGen, Inc.)H-Index: 16
#2Nathan Fishkin (ImmunoGen, Inc.)H-Index: 9
Last. Ravi V. J. Chari (ImmunoGen, Inc.)H-Index: 30
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The promise of tumor-selective delivery of cytotoxic agents in the form of antibody-drug conjugates (ADCs) has now been realized, evidenced by the approval of two ADCs, both of which incorporate highly cytotoxic tubulin-interacting agents, for cancer therapy. An ongoing challenge remains in identifying potent agents with alternative mechanisms of cell killing that can provide ADCs with high therapeutic indices and favorable tolerability. Here we describe the development of a new class of potent ...
50 CitationsSource
#1Jose F. Ponte (ImmunoGen, Inc.)H-Index: 10
#2Xiuxia Sun (ImmunoGen, Inc.)H-Index: 6
Last. John M. Lambert (ImmunoGen, Inc.)H-Index: 52
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Antibody-drug conjugates (ADCs) have become a widely investigated modality for cancer therapy, in part due to the clinical findings with ado-trastuzumab emtansine (Kadcyla). Ado-trastuzumab emtansine utilizes the Ab-SMCC-DM1 format, in which the thiol-functionalized maytansinoid cytotoxic agent, DM1, is linked to the antibody (Ab) via the maleimide moiety of the heterobifunctional SMCC linker. The pharmacokinetic (PK) data for ado-trastuzumab emtansine point to a faster clearance for the ADC tha...
33 CitationsSource
#1Rajeeva Singh (ImmunoGen, Inc.)H-Index: 23
#2Yulius Setiady (ImmunoGen, Inc.)H-Index: 15
Last. Wayne C. Widdison (ImmunoGen, Inc.)H-Index: 15
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A triglycyl peptide linker (CX) was designed for use in antibody-drug conjugates (ADCs), aiming to provide efficient release and lysosomal efflux of cytotoxic catabolites within targeted cancer cells. ADCs comprising anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-epidermal growth factor receptor (anti-EGFR) antibodies with maytansinoid payloads were prepared using CX or a non-cleavable SMCC linker (CX and SMCC ADCs). The in vitro cytotoxic activities of CX and SMCC ADCs were simila...
15 CitationsSource
#1Bart De Goeij (Genmab)H-Index: 7
#2John M. Lambert (ImmunoGen, Inc.)H-Index: 52
The clinical success of Adcetris ® (brentuximab vedotin) and Kadcyla ® (ado-trastuzumab emtansine) has sparked clinical development of novel ADCs. These powerful anti-cancer agents are designed to allow specific targeting of highly potent cytotoxic agents to tumor cells while sparing healthy tissues. Despite the use of tumor-specific antibodies, the emerging clinical data with ADCs indicates that adverse effects frequently occur before ADCs have reached their optimal therapeutic dose, resulting ...
154 CitationsSource
5 CitationsSource
#1Tim JonesH-Index: 8
Last. Matthew BakerH-Index: 18
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An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a –mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclona...
41 CitationsSource
15 CitationsSource