John M. Lambert
ImmunoGen, Inc.
CytotoxicityPharmacokineticsImmunotoxinAntigenMolecular biologyCytotoxic T cellAntibodyChemistryConjugateImmunologyIn vivoRicinAntibody-drug conjugateImmunoconjugateMaytansinoidCancer researchMonoclonal antibodyBiochemistryMedicineBiologyPharmacology
Publications 103
#1Yulius Setiady (ImmunoGen, Inc.)H-Index: 15
#2Peter U. Park (ImmunoGen, Inc.)H-Index: 6
Last. Thomas Chittenden (ImmunoGen, Inc.)H-Index: 3
view all 13 authors...
EGFR is an attractive target for the treatment of a variety of solid tumors because of its role as a driver oncogene and high level of expression. Four EGFR-targeting agents, including two antibodies (Abs), have been approved for clinical use. Despite anti-tumor benefits, inhibition of EGFR pathway is associated with significant dermatologic toxicities; resistance to EGFR antagonists also develops. To enhance potency with comparable or better tolerability, we developed IMGN289, an EGFR-targeting...
4 CitationsSource
#1Thomas Chittenden (ImmunoGen, Inc.)H-Index: 3
#2Yulius Setiady (ImmunoGen, Inc.)H-Index: 15
Last. John M. Lambert (ImmunoGen, Inc.)H-Index: 52
view all 11 authors...
NSCLC accounts for approximately 85% of all lung cancers. Based on tumor histology, NSCLC can be subdivided into adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC), which account for 40%, 25-30% and 10-15% of NSCLC cases, respectively. In a fraction of AC cases, driver oncogenes have been identified that enable effective treatment with targeted therapies. For most NSCLC cases, however, etiology is still unknown and effective targeted therapies have yet to be achie...
1 CitationsSource
#1John M. Lambert (ImmunoGen, Inc.)H-Index: 52
#2Veronique BlancH-Index: 1
Last. Anne BousseauH-Index: 1
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CD19 is a 95 kDa type 1 transmembrane glycoprotein whose expression is highly restricted to cells of B-lineage. CD19 expression is maintained in B-lineage cells that have undergone malignant transformation. Several approaches to exploit anti-CD19 monoclonal antibodies to treat B cell malignancies are being evaluated, including “naked” antibodies, bispecific antibodies, and immunoconjugates. SAR3419 is an ADC that is composed of a humanized monoclonal IgG1 anti-CD19 antibody (huB4) attached to a ...
1 CitationsSource
#1John M. Lambert (ImmunoGen, Inc.)H-Index: 52
#2James J. O'leary (ImmunoGen, Inc.)H-Index: 8
Last. Victor S. Goldmacher (ImmunoGen, Inc.)H-Index: 55
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CD56, also known as neural cell adhesion molecule (NCAM), is a type 1 transmembrane glycoprotein that is expressed on neuronal tissue, skeletal and heart muscle, various cells of neuroendocrine origin, as well as natural killer cells and a subset of T cells. The extracellular domain comprises five immunoglobulin-like domains and two fibronectin domains. The molecule is thought to play an important role in cell–cell and cell–matrix interactions, especially in early development. A number of differ...
5 CitationsSource
#1Alain BeckH-Index: 56
#2John M. Lambert (ImmunoGen, Inc.)H-Index: 52
Last. Kedan Lin (Genentech)H-Index: 14
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The 4th World Antibody Drug Conjugate (WADC) Summit, organized by Hanson Wade was held on February 29‑March 1, 2012 in Frankfurt, Germany, which was also the location for the Antibody Drug Conjugate Summit Europe held in February 2011. During the one year between these meetings, antibody drug conjugates (ADCs) have confirmed their technological maturity and their clinical efficacy in oncology. Brentuximab vedotin (ADCETRISTM) gained approval by the US Food and Drug Administration in August 2011 ...
33 CitationsSource
#1Hans K. Erickson (ImmunoGen, Inc.)H-Index: 17
#2John M. Lambert (ImmunoGen, Inc.)H-Index: 52
The concept of treating cancer with antibody-drug conjugates (ADCs) has gained momentum with the favorable activity and safety of trastuzumab emtansine (T-DM1), SAR3419, and lorvotuzumab mertansine (IMGN901). All three ADCs utilize maytansinoid cell-killing agents which target tubulin and suppress microtubule dynamics. Each ADC utilizes a different optimized chemical linker to attach the maytansinoid to the antibody. Characterizing the absorption, distribution, metabolism, and excretion (ADME) o...
88 CitationsSource
#1Anas Younes (University of Texas MD Anderson Cancer Center)H-Index: 92
#2Stella K. Kim (University of Texas MD Anderson Cancer Center)H-Index: 20
Last. Leo I. Gordon (NU: Northwestern University)H-Index: 85
view all 14 authors...
Purpose We determine the maximum-tolerated dose (MTD), pharmacokinetics, safety, and preliminary efficacy of SAR3419, an antibody-drug conjugate targeting CD19, in a first-in-man phase I clinical trial in patients with relapsed lymphoma. Patients and Methods Patients with relapsed CD19+ B-cell lymphoma were treated with escalating doses of SAR3419 given by intravenous infusion once every 21 days. Results Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m2. The med...
131 CitationsSource
#1Simona LapusanH-Index: 18
Last. Jean Pierre Marie (UPMC: Pierre-and-Marie-Curie University)H-Index: 9
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The efficacy of anti-CD33 immunoconjugates had been previously demonstrated for gemtuzumab-ozogamicin. AVE9633 is an anti-CD33-maytansine conjugate created by ImmunoGen Inc. Phase I trials of AVE9633 were performed in patients with AML to evaluate tolerability, pharmacokinetics and pharmacodynamics. Three phase I studies of AVE9633 were performed in 54 patients with refractory/relapsed AML, evaluating drug infusion on day 1 of a 21-day cycle (Day 1 study), day 1 and 8 (Day 1/8 study) and day 1, ...
79 CitationsSource
#1Bertrand CoiffierH-Index: 101
#2Franck MorschhauserH-Index: 63
Last. Vincent RibragH-Index: 56
view all 12 authors...
8057 Background: The recommended dose (RD) of SAR3419 administered intravenously every 3 weeks (q3w) for 6 cycles is 160 mg/m2 and is 55 mg/m2 when administered weekly (q1w) for 8-12 doses. Reversible corneal deposits were dose limiting (DLT) in the q3w schedule. The q1w schedule was well tolerated and active. However, based on the occurrence of late/cumulative adverse events (AE) at the RD supported by pharmacokinetic (PK) analyses showing ADC plasma accumulation after 4 weekly doses, an optimi...
6 CitationsSource
#1Victor S. Goldmacher (ImmunoGen, Inc.)H-Index: 55
#2Thomas Chittenden (ImmunoGen, Inc.)H-Index: 38
Last. John M. Lambert (ImmunoGen, Inc.)H-Index: 52
view all 5 authors...
Abstract The state-of-the-art of antibody–drug conjugates (ADCs) for cancer treatment is discussed: the rationale, and considerations in selection of the target antigen, the linker, and the attached cytotoxic agent. Preclinical and clinical experience with ADCs is also discussed.
7 CitationsSource