A5001112274- Cancer Research and Treatments
- Glioma Diagnosis and Treatment
- Toxin Mechanisms and Immunotoxins
- Neuroblastoma Research and Treatments
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer, Stress, Anesthesia, and Immune Response
- Radiopharmaceutical Chemistry and Applications
- PARP inhibition in cancer therapy
- Cytokine Signaling Pathways and Interactions
- Pancreatitis Pathology and Treatment
- Estrogen and related hormone effects
- Inflammatory Biomarkers in Disease Prognosis
- Health Systems, Economic Evaluations, Quality of Life
- Pancreatic and Hepatic Oncology Research
- Statistical Methods in Clinical Trials
- Biosimilars and Bioanalytical Methods
- Advanced Electron Microscopy Techniques and Applications
- Cholinesterase and Neurodegenerative Diseases
- Nanoparticle-Based Drug Delivery
- Coordination Chemistry and Organometallics
- Coccidia and coccidiosis research
- Tryptophan and brain disorders
- Radiomics and Machine Learning in Medical Imaging
Pharma Medica Research (Canada)
2021-2024
University of Miami
2021
Northwestern Memorial Hospital
2012
Lurie Children's Hospital
2012
Northwestern University
2012
Abstract Background MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R overexpressed GBM as well cells of the tumor microenvironment. High expression associated with poor clinical outcomes. Methods MDNA55-05 open-label, single-arm phase IIb study (rGBM) patients aggressive form (de novo IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. was administered intratumorally single dose...
Abstract Purpose: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified (mRANO) criteria as well quantified association between progression-free (PFS) overall survival (OS) an trial recurrent glioblastoma (rGBM). Patients Methods: A total of 47 patients with rGBM were enrolled a prospective phase II convection-enhanced delivery IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements created...
2513 Background: MDNA55 is an engineered IL-4 fused to pseudomonas exotoxin A being developed for GBM, aggressive, universally fatal disease. No curative therapy exists and 75% of patients are not eligible resection at recurrence. targets IL4R overexpressed in the immunosuppressive tumor microenvironment, high expression associated with poor survival outcomes GBM. Ph 2b trial was completed rGBM using convection-enhanced delivery bypass BBB. Here we report results from comparison against a...
Abstract BACKGROUND Drug development in recurrent glioblastoma multiforme (rGBM) is challenging. For randomized controlled trials (RCTs) short survival horizons and limited life-prolonging treatment options may delay accrual introduce bias through differential dropout of control patients. Comparing results a single-arm Phase 2b trial intratumoral delivery MDNA55 (an interleukin-4 receptor targeted fusion protein) to an external arm, we sought early efficacy insights consideration by the FDA...
2039 Background: IL4 receptor (IL4R) is frequently and intensely expressed on a variety of human cancers associated with poor survival outcomes. Determining the role IL4R biomarker in glioblastoma (GBM) will be important for treatment targeted therapies such as fusion toxin MDNA55. Methods: A classification IL4Rα expression GBM tissues by H-Score was developed using validated immunohistochemistry-based approach. MDNA55-05 an open-label study MDNA55 administered intratumorally via convection...
Abstract Glioblastoma (GBM) is an aggressive brain tumor with a median overall survival (mOS) of 14 months. Treatment options are limited no new approved therapies over the past 3 decades and standard care for majority patients (> 90%) who experience recurrence. GBM has highly immune suppressive microenvironment (TME) comprising myeloid derived suppressor cells (MDSCs) associated macrophages (TAMs) that capable suppressing activity anti-cancer CD8+ T NK cells. We have engineered...
e14546 Background: The efficacy and safety of recombinant human IL-2 (rhIL-2; Proleukin) to treat certain cancers is limited by a short half-life, marked toxicity selective high affinity binding IL2Ra over IL2Rb, resulting in preferential activation suppressive Tregs. In contrast, MDNA11 has been engineered as long-acting superkine with IL2Rb receptor selectivity, anti-cancer effector immune cell activation. Methods: was characterized both vitro vivo studies including assessment kinetics...
Abstract BACKGROUND MDNA55 is an IL4R-targeted toxin in development for GBM, a universally fatal disease. IL4R over-expressed the tumor microenvironment, and high expression associated with poor outcomes GBM. METHOD MDNA55-05 open-label, single-arm study of delivered by CED as single treatment rGBM patients at 1st or 2nd recurrence aggressive form GBM (de novo IDH wild-type, not-resectable recurrence, ~ 50% expressing levels IL4R). Primary endpoint mOS, secondary includes impact status on...
Abstract MDNA55, an IL4R-directed toxin, is being studied in a Phase 2b trial recurrent GBM (rGBM) patients at first or second relapse. MDNA55 co-infused with Gadolinium-based contrast agent and delivered as single intratumoral infusion using Convection Enhanced Delivery (CED). Primary endpoint median Overall Survival (mOS) secondary objective response rate (ORR) assessed by mRANO-based criteria incorporating advanced imaging modalities. Enrollment complete (n=46). Current safety data show...
3036 Background: Use of IL-2 (Proleukin) remains limited due to its short half-life, toxicity, and ability preferentially activate Tregs resulting in unwanted immune suppression. Approaches reduce binding CD25 (IL2α), such as pegylation techniques, also results reduced affinity CD122 (IL2β). To bypass these limitations, we engineered MDNA11, an Superkine containing core mutations diminish while increasing CD122. increase MDNA11 was fused albumin scaffold, which is known allow accumulation at...
Abstract BACKGROUND MDNA55 is an IL4R-targeted toxin in development for treatment of recurrent glioblastoma (rGBM). binds to IL4R expressed by tumor cells and non-malignant the microenvironment. METHOD MDNA55-05 was open-label, single-arm study delivered CED as a single patients with 1st or 2nd recurrence following de novo GBM, IDH wild type status not indicated resection at relapse. Dose volumes (up 60mL) concentration (1.5 9.0 μg/mL) were studied. RESULTS showed acceptable safety profile...
<p>Medicenna Imaging Charter for Independent Radiologic Review of MDNA55-05.</p>
<p>Correlation between mRANO-defined PFS and OS excluding patients with > 120 days. (top) Correlation radiographic using the mRANO criteria applied to local measurements for who died. (bottom) IRF-determined Open circles = were censored (not used in correlation analysis, only visualization purposes).</p>
<p>Correlation between duration of clinical benefit (DOCB) and overall survival (OS) for the standard RANO, iRANO, mRANO criteria. (A) Correlation radiographic DOCB using RANO criteria applied to local measurements OS patients who died. (B) iRANO (C) (D) IRF-determined (E) (F) Solid circles = progressed. Open were censored (not used in correlation analysis, only visualization purposes).</p>
<p>Correlation between mRANO-defined PFS and OS excluding patients with > 120 days. (top) Correlation radiographic using the mRANO criteria applied to local measurements for who died. (bottom) IRF-determined Open circles = were censored (not used in correlation analysis, only visualization purposes).</p>
<p>iRANO Response Rubric.</p>
<div>AbstractPurpose:<p>The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified (mRANO) criteria as well quantified association between progression-free (PFS) overall survival (OS) an trial recurrent glioblastoma (rGBM).</p>Patients Methods:<p>A total of 47 patients with rGBM were enrolled a prospective phase II convection-enhanced delivery IL4R-targeted immunotoxin (MDNA55-05, NCT02858895)....
<p>Supplemental Figure Captions</p>
<p>Correlation between duration of clinical benefit (DOCB) and overall survival (OS) for the standard RANO, iRANO, mRANO criteria. (A) Correlation radiographic DOCB using RANO criteria applied to local measurements OS patients who died. (B) iRANO (C) (D) IRF-determined (E) (F) Solid circles = progressed. Open were censored (not used in correlation analysis, only visualization purposes).</p>
<p>iRANO Response Rubric.</p>
<p>mRANO Response Rubric.</p>
<p>Supplemental Figure Captions</p>
<p>Medicenna Imaging Charter for Independent Radiologic Review of MDNA55-05.</p>
<p>mRANO Response Rubric.</p>