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.
Purpose The folate receptor (FR) has emerged as an interesting diagnostic and therapeutic drug target with many potential applications in oncologic and inflammatory disorders. It was therefore the aim of this study to develop a folate-derived Ga-68-based positron emission tomography (PET) imaging tracer that is straightforward to radiolabel and could be broadly used in clinical studies. We validated its target binding affinity and specificity and compared it to [99mTc]EC20, the folate single-pho...
BACKGROUND Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors. METHODS Patients received IMGN853 on day 1 of a 21-day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose-limiting toxicity or progression. Dose escalation commenced in single-patient cohorts for the first 4 planned dose...
: Anticancer nanotherapeutics have shown mixed results in clinical trials, raising the questions of whether imaging should be used to i) identify patients with a higher likelihood of nanoparticle accumulation, ii) assess nanotherapeutic efficacy before traditional measures show response, and iii) guide adjuvant treatments to enhance therapeutic nanoparticle (TNP) delivery. Here we review the use of a clinically approved MRI nanoparticle (ferumoxytol, FMX) to predict TNP delivery and efficacy. It...
4093Background: PRRT represents a step change in NET management, significantly improving survival. However, objective response to PRRT, approximately 20%, is poor. There are no predictive biomarker...
Last. Michael J. Birrer(Sarah Cannon Research Institute)H-Index: 109
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PurposeThis phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody–drug conjugate consisting of a humanized anti–folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer.Patients and MethodsPatients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN85...
Antibody–drug conjugate (ADCs), which aim to target highly cytotoxic drugs specifically to cancer cells, are one of the fastest growing classes of anticancer therapeutics, with more than 50 such agents currently in clinical trials. This Review discusses lessons learned and emerging strategies in the development of ADCs, including aspects such as target selection, the development of warheads, the optimization of linkers and new conjugation chemistries, and provides an overview of agents that are ...
PurposeFarletuzumab is a humanized monoclonal antibody that binds to folate receptor-α, which is highly expressed in ovarian carcinoma and largely absent from normal tissue. Farletuzumab was investigated in a double-blind, randomized phase III study in platinum-sensitive ovarian cancer.Patients and MethodsEligible patients had first recurrent ovarian cancer 6-24 months following completion of platinum-taxane chemotherapy. All patients received carboplatin plus paclitaxel or docetaxel (for six cy...
#2Vladimir Neychev(NIH: National Institutes of Health)H-Index: 14
Last. Electron Kebebew(NIH: National Institutes of Health)H-Index: 85
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PurposeGastro-entero-pancreatic neuroendocrine tumors (GEPNETs) are increasing in incidence, and accurate staging is important for selecting the appropriate treatment. 68Ga-DOTATATE imaging is a promising approach for detecting GEPNETs and could help in selecting optimal therapeutic strategies. The aim of this study was to prospectively determine the clinical utility of 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) in detecting unknown primary and metastatic GEPNETs.P...
The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co...
Last. Daniel A. Pryma(UPenn: University of Pennsylvania)H-Index: 26
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The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the ...
Last. Weibo Cai(UW: University of Wisconsin-Madison)H-Index: 91
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Immuno-positron emission tomography (immunoPET) is a paradigm-shifting molecular imaging modality combining the superior targeting specificity of monoclonal antibody (mAb) and the inherent sensitivity of PET technique. A variety of radionuclides and mAbs have been exploited to develop immunoPET probes, which has been driven by the development and optimization of radiochemistry and conjugation strategies. In addition, tumor-targeting vectors with a short circulation time (e.g., Nanobody) or with ...
#2Elena Cojocaru(ICR: Institute of Cancer Research)H-Index: 4
Last. Udai Banerji(ICR: Institute of Cancer Research)H-Index: 43
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Folate receptor α (FRα) came into focus as an anticancer target many decades after the successful development of drugs targeting intracellular folate metabolism, such as methotrexate and pemetrexed. Binding to FRα is one of several methods by which folate is taken up by cells; however, this receptor is an attractive anticancer drug target owing to the overexpression of FRα in a range of solid tumours, including ovarian, lung and breast cancers. Furthermore, using FRα to better localize effective...
TRA-1-60 (TRA) is a cell-surface antigen implicated in drug resistance, relapse and recurrence. Its expression has been reported in breast, prostate, pancreatic, ovarian tumors and follicular lymphoma, which paved the development of the therapeutic antibody, Bstrongomab (Bsg) and its drug conjugates. Because patient selection is critical to achieve clinical benefit, a non-invasive imaging agent to select TRA+ lesions in patients is needed. Herein, we report the development of the immunopositron ...
#1Sridhar Nimmagadda(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 29
#2Marie-France Penet(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 23
Ovarian cancer is a leading cause of death from gynecological malignancies. Although the prognosis is quite favorable if detected at an early stage, the vast majority of cases are diagnosed at an advanced stage, when 5-year survival rates are only 30-40%. Most recurrent ovarian tumors are resistant to traditional therapies underscoring the need for new therapeutic options. Theranostic agents, that combine diagnostic and therapeutic capabilities, are being explored to better detect, diagnose and ...