Steven Boule
ImmunoGen, Inc.
Receptor tyrosine kinasePharmacokineticsCancerAntigenCellCell signalingAntibodyReceptorProteasesChemistryConjugateIn vitroIn vivoEpithelial cell adhesion moleculeAntibody-drug conjugateBiodistributionMetastasisMaytansinoidDrugFolate receptorPopulationCancer researchPotencyMedicineBiologyImmune systemPharmacologyDistribution (pharmacology)
Publications 5
#1Katharine C. LaiH-Index: 9
#2Min LiH-Index: 4
Last. Kerry DonahueH-Index: 2
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With cancer among the leading causes of death worldwide, the search for better, personalized treatments is imperative. Novel techniques such as next generation sequencing have identified many assayable genetic biomarkers associated with cancer in patient samples. The tyrosine kinase receptor cMet is one such biomarker that is upregulated in various solid tumors and associated with poor prognosis, disease progression and metastasis. While most patients with elevated cMet show increased levels thr...
#2Leanne LanieriH-Index: 8
Last. Richard J. GregoryH-Index: 44
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The majority of antibody-drug conjugates (ADCs) with maytansinoid payloads in development are linked via lysine residues and target an average drug-antibody ratio (DAR) of 3.5. These ADCs demonstrate substantial preclinical potency while maintaining good biophysical and pharmacological properties. However, some targets are expressed in normal tissues at levels that result in target-mediated drug disposition (TMDD), which can impact systemic and tumor ADC exposure and tumor penetration. For targe...
#1Leanne Lanieri (ImmunoGen, Inc.)H-Index: 8
#2Rassol Laleau (ImmunoGen, Inc.)H-Index: 3
Last. Richard Gregory (ImmunoGen, Inc.)H-Index: 1
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Antibody-drug conjugates (ADCs) are designed to deliver a potent cytotoxic payload directly to tumors, thus limiting exposure in normal tissues. However, target antigen expression on normal tissues can lead to lower systemic ADC exposures, resulting in sub-efficacious concentrations at the tumor site as well as heterogeneous distribution within tumors. Traditional preclinical efficacy studies performed in rodent models using ADCs with non-cross-reactive antibodies have been of limited translatio...
#1Yimao Liu (ImmunoGen, Inc.)
#1Yimao LiuH-Index: 5
Last. Stuart W. HicksH-Index: 15
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Epithelial Cell Adhesion Molecule (EpCAM) is a glycosylated, 40-kDa type I transmembrane protein that plays a role in cell adhesion and cell signaling. EpCAM is an attractive target for antibody drug conjugate (ADC) development due to its overexpression on a variety of tumors of epithelial origin, including lung, colon, breast, ovarian, prostate and pancreatic cancers. In addition, EpCAM is enriched on tumor-initiating cells (TICs), which are often resistant to conventional cancer therapies. As ...
#1Leanne Lanieri (ImmunoGen, Inc.)H-Index: 8
#2Steven Boule (ImmunoGen, Inc.)
Last. Richard Gregory (ImmunoGen, Inc.)H-Index: 1
view all 12 authors...
Among the many factors determining the clinical efficacy of antibody-drug conjugates (ADCs) are dose and schedule, target antigen expression (both on tumor and normal tissues), antibody affinity, drug-to-antibody ratio (DAR), bystander killing activity, the ability of the ADC to penetrate and distribute into the tumor, and interaction with the host immune system. Traditional ADC efficacy studies use cell line-derived (CDX) or patient-derived xenografts (PDX) implanted into immuno-compromised mic...