Yulius Setiady
ImmunoGen, Inc.
CancerAntigenCytotoxic T cellAntibodyAutoantibodyChemistryConjugateIn vitroImmunologyIn vivoAntibody-drug conjugateAutoimmune diseaseMaytansinoidAutoimmunityLinkerCancer researchBiochemistryMedicineIL-2 receptorBiologyImmune systemCancer cell
44Publications
15H-index
988Citations
Publications 44
Newest
#1Jose F. PonteH-Index: 10
#2Leanne LanieriH-Index: 8
Last. Greg M. Thurber (UM: University of Michigan)H-Index: 23
view all 15 authors...
Several antibody-drug conjugates (ADCs) showing strong clinical responses in solid tumors target high expression antigens (HER2, TROP2, Nectin-4, and folate receptor alpha/FRα). Highly expressed tumor antigens often have significant low-level expression in normal tissues, resulting in the potential for target-mediated drug disposition (TMDD) and increased clearance. However, ADCs often do not cross-react with normal tissue in animal models used to test efficacy (typically mice), and the impact o...
3 CitationsSource
#1Olga Ab (ImmunoGen, Inc.)H-Index: 10
#2Laura M. Bartle (ImmunoGen, Inc.)H-Index: 13
Last. Eric H. Westin (ImmunoGen, Inc.)
view all 18 authors...
Folate Receptor alpha (FRα) is an attractive antibody drug conjugate (ADC) target due to its over expression in multiple epithelial malignancies including ovarian, endometrial, triple negative breast, and non-small cell lung cancer, with limited expression on normal tissues. IMGN853 (i.e., mirvetuximab soravtansine and M9346A-sulfo-SPDB-DM4), a FRα targeting ADC, is currently in phase III (MIRASOL) clinical evaluation as monotherapy in patients with platinum-resistant epithelial ovarian cancer w...
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#1Juliet Costoplus (ImmunoGen, Inc.)H-Index: 4
#2Karen Veale (ImmunoGen, Inc.)H-Index: 4
Last. Wayne C. Widdison (ImmunoGen, Inc.)H-Index: 15
view all 17 authors...
A new type of antibody–drug conjugate (ADC) has been prepared that contains a sulfur-bearing maytansinoid attached to an antibody via a highly stable tripeptide linker. Once internalized by cells, proteases in catabolic vesicles cleave the peptide of the ADC’s linker causing self-immolation that releases a thiol-bearing metabolite, which is then S-methylated. Conjugates were prepared with peptide linkers containing only alanyl residues, which were all l isomers or had a single d residue in one o...
9 CitationsSource
#1Wei Li (ImmunoGen, Inc.)H-Index: 3
#2Karen Veale (ImmunoGen, Inc.)H-Index: 4
Last. Wayne C. Widdison (ImmunoGen, Inc.)H-Index: 15
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Antibody–drug conjugates (ADCs) that incorporate the exatecan derivative DXd in their payload are showing promising clinical results in solid tumor indications. The payload has an F-ring that also contains a second chiral center, both of which complicate its synthesis and derivatization. Here we report on new camptothecin-ADCs that do not have an F-ring in their payloads yet behave similarly to DXd-bearing conjugates in vitro and in vivo. This simplification allows easier derivatization of campt...
6 CitationsSource
#1Katie E. Archer (ImmunoGen, Inc.)H-Index: 4
#2Emily E. Reid (ImmunoGen, Inc.)H-Index: 4
Last. Michael L. Miller (ImmunoGen, Inc.)H-Index: 17
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Indolinobenzodiazepine DNA alkylators (IGNs) are the cytotoxic payloads in antibody–drug conjugates (ADCs) currently undergoing Phase I clinical evaluation (IMGN779, IMGN632, and TAK164). These ADCs possess linkers that have been incorporated into a central substituted phenyl spacer. Here, we present an alternative strategy for the IGNs, linking through a carbamate at the readily available N-10 amine present in the monoimine containing dimer. As a result, we have designed a series of N-10 linked...
5 CitationsSource
#1Leanne Lanieri (ImmunoGen, Inc.)H-Index: 8
#2Rassol Laleau (ImmunoGen, Inc.)H-Index: 3
Last. Richard Gregory (ImmunoGen, Inc.)H-Index: 1
view all 14 authors...
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...
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#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...
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#1Yelena Kovtun (ImmunoGen, Inc.)H-Index: 19
#2Gregory E. Jones (ImmunoGen, Inc.)H-Index: 4
Last. Thomas Chittenden (ImmunoGen, Inc.)H-Index: 38
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The outlook for patients with refractory/relapsed acute myeloid leukemia (AML) remains poor, with conventional chemotherapeutic treatments often associated with unacceptable toxicities, including severe infections due to profound myelosuppression. Thus there exists an urgent need for more effective agents to treat AML that confer high therapeutic indices and favorable tolerability profiles. Because of its high expression on leukemic blast and stem cells compared with normal hematopoietic stem ce...
63 CitationsSource
#1Wayne C. WiddisonH-Index: 15
#2Juliet CostoplusH-Index: 4
Last. Ravi V. J. ChariH-Index: 30
view all 11 authors...
Antibodies targeting surface antigens on cancer cells typically have progressively lower access to tumor cells that are further removed from blood vessels. Also, the antibody will not bind to cells in the tumor mass that do not express antigen, including stromal cells of the tumor, many of which reportedly aid in the survival or metastasis of cancer cells. ADCs can bind to antigen positive cancer cells, after which they are internalized and catabolized to release one or more cytotoxic metabolite...
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