Qifeng Qiu
ImmunoGen, Inc.
CytotoxicityAntigenCellCytotoxic T cellAntibodyChemistryBystander effectConjugateTherapeutic indexIn vitroIn vivoAntibody-drug conjugateBiodistributionMaytansinoidPeptideDrugFolate receptorLinkerCancer researchBiochemistryMedicineCell cultureCancer cellPharmacology
17Publications
7H-index
147Citations
Publications 17
Newest
#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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#1Ian Nessler (UM: University of Michigan)H-Index: 6
#2Eshita Khera (UM: University of Michigan)H-Index: 8
Last. Greg M. ThurberH-Index: 23
view all 12 authors...
Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied by the seven current FDA approved antibody-drug conjugates (ADCs). However, a variety of pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering the development of new drugs. Here, we use a series of Prostate-Specific Membrane Antigen (PSMA)-binding single-domain (Humabody®) ADC constructs to demonstrate...
12 CitationsSource
#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
#1Stuart W. Hicks (ImmunoGen, Inc.)H-Index: 15
#2Chiara Tarantelli (USI: University of Lugano)H-Index: 12
Last. Francesco Bertoni (USI: University of Lugano)H-Index: 78
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Antibody-drug conjugates (ADC) are a novel way to deliver potent cytotoxic compounds to cells expressing a specific antigen. Four ADC targeting CD19, including SAR3419 (coltuximab ravtansine), have entered clinical development. Here, we present huB4-DGN462, a novel ADC based on the SAR3419 anti-CD19 antibody linked via sulfo-SPDB to the potent DNA-alkylating agent DGN462. huB4-DGN462 had improved in vitro anti-proliferative and cytotoxic activity compared to SAR3419 across multiple B-cell lympho...
9 CitationsSource
#1Laura A. Laviolette (ImmunoGen, Inc.)
Last. Dan SnellH-Index: 2
view all 24 authors...
DARPin® molecules are small engineered proteins, derived from natural ankyrin repeat proteins that are selected to bind to specific targets with high affinity. Individual DARPin® molecules can be linked together genetically in order to create multi-specific drug molecules. This versatility of DARPin® molecules makes them an attractive alternative to antibodies for the development of drug conjugates. We have developed DARPin® drug conjugates (DDCs) using a model EGFR multi-specific DARPin® molecu...
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#1Leanne Lanieri (ImmunoGen, Inc.)H-Index: 8
#2Steven Boule (ImmunoGen, Inc.)
Last. Richard Gregory (ImmunoGen, Inc.)H-Index: 1
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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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#1Michael L. Miller (ImmunoGen, Inc.)H-Index: 17
#2Manami Shizuka (ImmunoGen, Inc.)H-Index: 4
Last. Ravi V. J. Chari (ImmunoGen, Inc.)H-Index: 30
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Tumor-selective delivery of cytotoxic agents in the form of antibody–drug conjugates (ADCs) is now a clinically validated approach for cancer treatment. In an attempt to improve the clinical success rate of ADCs, emphasis has been recently placed on the use of DNA–cross-linking pyrrolobenzodiazepine compounds as the payload. Despite promising early clinical results with this class of ADCs, doses achievable have been low due to systemic toxicity. Here, we describe the development of a new class o...
14 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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#1Qifeng QiuH-Index: 7
#2Rui WuH-Index: 4
Last. Erica HongH-Index: 4
view all 15 authors...
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