Xiuxia Sun
ImmunoGen, Inc.
CytotoxicityPharmacokineticsAntigenMolecular biologyCytotoxic T cellAntibodyChemistryConjugateIn vitroImmunologyIn vivoAntibody-drug conjugateMaytansinoidFolate receptorLinkerCancer researchMonoclonal antibodyBiochemistryMedicineCell cultureCancer cellPharmacology
Publications 23
#1Carl Uli Bialucha (Novartis)H-Index: 11
#2Scott D. Collins (Novartis)H-Index: 2
Last. Emma Lees (Novartis)H-Index: 29
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Despite an improving therapeutic landscape, significant challenges remain in treating the majority of patients with advanced ovarian or renal cancer. We identified the cell–cell adhesion molecule cadherin-6 ( CDH6 ) as a lineage gene having significant differential expression in ovarian and kidney cancers. HKT288 is an optimized CDH6-targeting DM4-based antibody–drug conjugate (ADC) developed for the treatment of these diseases. Our study provides mechanistic evidence supporting the importance o...
23 CitationsSource
#1Xiuxia Sun (ImmunoGen, Inc.)H-Index: 6
#2Jose F. Ponte (ImmunoGen, Inc.)H-Index: 10
Last. John M. LambertH-Index: 52
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Antibody–drug conjugates (ADCs) are being actively pursued as a treatment option for cancer following the regulatory approval of brentuximab vedotin (Adcetris) and ado-trastuzumab emtansine (Kadcyla). ADCs consist of a cytotoxic agent conjugated to a targeting antibody through a linker. The two approved ADCs (and most ADCs now in the clinic that use a microtubule disrupting agent as the payload) are heterogeneous conjugates with an average drug-to-antibody ratio (DAR) of 3–4 (potentially ranging...
58 CitationsSource
#1Nicholas C. YoderH-Index: 15
#2Chen BaiH-Index: 6
Last. Thomas A. KeatingH-Index: 5
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ADCs are widely studied for cancer therapy, with numerous agents in preclinical and clinical development embodying a wide array of targets, linker chemistries, and cytotoxic effector classes. A fourth element of ADC design that has received much attention recently is the site of conjugation of the cytotoxic molecule to the antibody. Historically, lysine- or interchain cysteine-directed conjugation has been used, but site-specific chemistries have become increasingly popular. Our previous evaluat...
#1Dilrukshi Vitharana (ImmunoGen, Inc.)H-Index: 2
#2Alan Wilhelm (ImmunoGen, Inc.)H-Index: 8
Last. Nathan Fishkin (ImmunoGen, Inc.)H-Index: 9
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Previously we have described the characterization of a proprietary class of indolino-benzodiazepine dimers, IGNs, with high potency against many cancer lines. Antibody-drug conjugates (ADCs) made with mono-imine containing IGNs were designed to only alkylate DNA and not cause DNA crosslinking. ADCs with the IGN linked via lysine residues of the antibody were shown to be highly potent and antigen specific. Here we apply our SeriMab site-specific technology platform, which employs N-terminal conju...
1 CitationsSource
#1Scott D. Collins (Novartis)H-Index: 2
#2Parmita Saxena (Novartis)H-Index: 4
Last. Carl Uli Bialucha (Novartis)H-Index: 11
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In an attempt to mine tumor versus normal mRNA expression datasets for novel tumor antigens, we identified the Cadherin-6 (CDH6) gene as frequently overexpressed in ovarian and renal cancers, while featuring a lineage-restricted normal tissue expression pattern. CDH6, also known as K-(kidney)-cadherin, is a member of the cadherin superfamily of calcium-dependent cell-cell adhesion molecules. We hypothesized that based on the combined observation of frequent overexpression of CDH6 in cancer and a...
#1Jose F. Ponte (ImmunoGen, Inc.)H-Index: 10
#2Xiuxia Sun (ImmunoGen, Inc.)H-Index: 6
Last. John M. Lambert (ImmunoGen, Inc.)H-Index: 52
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Antibody-drug conjugates (ADCs) have become a widely investigated modality for cancer therapy, in part due to the clinical findings with ado-trastuzumab emtansine (Kadcyla). Ado-trastuzumab emtansine utilizes the Ab-SMCC-DM1 format, in which the thiol-functionalized maytansinoid cytotoxic agent, DM1, is linked to the antibody (Ab) via the maleimide moiety of the heterobifunctional SMCC linker. The pharmacokinetic (PK) data for ado-trastuzumab emtansine point to a faster clearance for the ADC tha...
33 CitationsSource
#1Xiuxia SunH-Index: 6
#2Jose F. PonteH-Index: 8
Last. John M. LambertH-Index: 16
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#1Katharine C. Lai (ImmunoGen, Inc.)H-Index: 9
#2Prerak Shah (ImmunoGen, Inc.)H-Index: 2
Last. Ravi V. J. Chari (ImmunoGen, Inc.)H-Index: 30
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Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA IMGN779, an antibody-drug conjugate (ADC) consisting of the anti-CD33 antibody, Z4681A, linked to the potent DNA-alkylating agent, DGN462, via a charged disulfide linker, sulfo-SPDB, is in development for the treatment of acute myeloid leukemia (AML). IMGN779 is highly active in vitro against AML cell lines and primary patient AML cells and causes complete regression of AML xenograft tumors at non-toxic doses in viv...
#1Olga Ab (ImmunoGen, Inc.)H-Index: 10
#2Kathleen R. Whiteman (ImmunoGen, Inc.)H-Index: 13
Last. John M. Lambert (ImmunoGen, Inc.)H-Index: 52
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A majority of ovarian and non–small cell lung adenocarcinoma cancers overexpress folate receptor α (FRα). Here, we report the development of an anti-FRα antibody–drug conjugate (ADC), consisting of a FRα-binding antibody attached to a highly potent maytansinoid that induces cell-cycle arrest and cell death by targeting microtubules. From screening a large panel of anti-FRα monoclonal antibodies, we selected the humanized antibody M9346A as the best antibody for targeted delivery of a maytansinoi...
79 CitationsSource
#1Olga Ab (ImmunoGen, Inc.)H-Index: 10
#2Laura M. Bartle (ImmunoGen, Inc.)H-Index: 13
Last. Victor S. Goldmacher (ImmunoGen, Inc.)H-Index: 55
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Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA IMGN853 comprises the anti-FR-α antibody M9346A conjugated to the cytotoxic maytansinoid molecule DM4 via a stable disulfide-containing linker, sulfo-SPDB. IMGN853 is currently in phase I clinical testing; promising clinical results were reported at ASCO 2013. To analyze determinants of the sensitivity of FR-α positive cells to IMGN853, we examined antigen density on the cell surface, internalization and processing of IMGN853,...