Wayne C. Widdison
ImmunoGen, Inc.
CytotoxicityAntigenCytotoxic T cellAntibodyChemistryConjugateTherapeutic indexIn vitroIn vivoLysineMetaboliteMaytansinoidPeptideLinkerCancer researchMonoclonal antibodyBiochemistryStereochemistryMedicineCancer cellPharmacology
42Publications
15H-index
2,706Citations
Publications 40
Newest
#1Olga Ab (ImmunoGen, Inc.)H-Index: 10
#2Laura M. Bartle (ImmunoGen, Inc.)H-Index: 13
Last. Eric H. Westin (ImmunoGen, Inc.)
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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
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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...
7 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...
2 CitationsSource
#1Nicholas C. YoderH-Index: 15
#2Chen BaiH-Index: 6
Last. John M. LambertH-Index: 52
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Antibody-drug conjugates are an emerging class of cancer therapeutics constructed from monoclonal antibodies conjugated with small molecule effectors. First generation molecules of this class often employed heterogeneous conjugation chemistry, but many site-specifically conjugated ADCs have been described recently. Here we undertake a systematic comparison of ADCs made with the same antibody and the same macrocyclic maytansinoid effector, but conjugated either heterogeneously at lysine residues ...
6 CitationsSource
#1Janet LauH-Index: 1
#2Paulin SalomonH-Index: 6
Last. Thomas A. KeatingH-Index: 5
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ImmunoGen’s newest antibody-drug conjugate (ADC) design uses the novel maytansinoid linker-payload, DM21-C that bears a peptidase/protease cleavable linker. These ADCs show good bystander killing of proximal antigen negative cells, suggesting the generation of cell-permeable catabolites. The goal of this study was to identify the catabolites generated upon incubation in antigen-positive cancer cells (both cell pellet and media), in mouse plasma, as well as in in vitro catabolic systems. Upon inc...
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#2Wayne C. WiddisonH-Index: 15
Last. Jan Pinkas (ImmunoGen, Inc.)H-Index: 11
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#1Chuan Shi (Janssen Pharmaceutica)H-Index: 3
#2Shalom Goldberg (Janssen Pharmaceutica)H-Index: 10
Last. Wenying Jian (Janssen Pharmaceutica)H-Index: 1
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Aim: Alternative scaffold proteins have emerged as novel platforms for development of therapeutic applications. One such application is in protein–drug conjugates (PDCs), which are analogous to ant...
6 CitationsSource
#1Chuan Shi (Janssen Pharmaceutica)H-Index: 3
#2Shalom Goldberg (Janssen Pharmaceutica)H-Index: 10
Last. Wenying Jian (Janssen Pharmaceutica)H-Index: 1
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Bioanalysis of antibody–drug conjugates (ADCs) is challenging due to the complex, heterogeneous nature of their structures and their complicated catabolism. To fully describe the pharmacokinetics (PK) of an ADC, several analytes are commonly quantified, including total antibody, conjugate, and payload. Among them, conjugate is the most challenging to measure, because it requires detection of both small and large molecules as one entity. Existing approaches to quantify the conjugated species of A...
6 CitationsSource
#1Wayne C. WiddisonH-Index: 15
#2Juliet CostoplusH-Index: 4
Last. Ravi V. J. ChariH-Index: 30
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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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#1Qifeng QiuH-Index: 7
#2Rui WuH-Index: 4
Last. Erica HongH-Index: 4
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