Jose F. Ponte
ImmunoGen, Inc.
CytotoxicityPharmacokineticsCancerAntigenCytotoxic T cellAntibodyChemistryConjugateIn vitroImmunologyIn vivoAntibody-drug conjugateMaytansinoidOvarian cancerLinkerFolate Receptor AlphaCancer researchBiochemistryMedicinePharmacology
32Publications
10H-index
327Citations
Publications 32
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.)
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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...
Source
#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
#1Emily E. Reid (ImmunoGen, Inc.)H-Index: 4
#2Katie E. Archer (ImmunoGen, Inc.)H-Index: 4
Last. Michael L. Miller (ImmunoGen, Inc.)H-Index: 17
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Abstract Antibody-drug conjugates (ADCs) incorporating potent indolinobenzodiazepine (IGN) DNA alkylators as the cytotoxic payload are currently undergoing clinical evaluation. The optimized design of these payloads consists of an unsymmetrical dimer possessing both an imine and an amine effectively eliminating DNA crosslinking and demonstrating improved tolerability in mice. Here we present an alternate approach to generating DNA alkylating ADCs by linking the IGN monomer with a biaryl system w...
2 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
view all 15 authors...
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
#1Christian Brand (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 15
#2Ahmad Sadique (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
Last. Thomas Reiner (Cornell University)H-Index: 39
view all 9 authors...
Background The folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), IMGN853, shows great antitumor activity against FRα-expressing tumors in vivo, but patient selection and consequently therapy outcome are based on immunohistochemistry. The aim of this study is to develop an antibody-derived immuno-PET imaging agent strategy for targeting FRα in ovarian cancer as a predictor of treatment success.
3 CitationsSource
#1Michael L. Miller (ImmunoGen, Inc.)H-Index: 17
#2Emily E. Reid (ImmunoGen, Inc.)H-Index: 4
Last. Ravi V. J. Chari (ImmunoGen, Inc.)H-Index: 30
view all 12 authors...
We have previously disclosed antibody-drug conjugates (ADCs) that incorporate our highly potent novel DNA alkylating indolino-benzodiazepine (termed IGN) pseudo dimer. ADCs of these DNA alkylating IGNs were found preclinically to demonstrate better tolerability and an improved overall therapeutic index (TI) compared with those of DNA crosslinking IGNs (Miller, et al., AACR 2017 #53). In our ongoing effort to further explore DNA alkylating effector molecules for ADCs, we disclose here a new class...
Source
#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...
Source
#1Gary Altwerger (Yale University)H-Index: 12
#2Elena Bonazzoli (Yale University)H-Index: 16
Last. Alessandro D. Santin (Yale University)H-Index: 62
view all 24 authors...
Source
#1Gary Altwerger (Yale University)H-Index: 12
#2Elena Bonazzoli (Yale University)H-Index: 16
Last. Alessandro D. Santin (Yale University)H-Index: 62
view all 25 authors...
Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. The in vitro cytotoxic activit...
10 CitationsSource