Antonia N. Policheni
A5026018646- Advanced Breast Cancer Therapies
- Cancer-related gene regulation
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Breast Cancer Treatment Studies
- Synthesis and Catalytic Reactions
- Lung Cancer Research Studies
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Genomics, phytochemicals, and oxidative stress
- RNA Interference and Gene Delivery
- Cancer-related molecular mechanisms research
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Advanced Biosensing Techniques and Applications
- Renin-Angiotensin System Studies
- Chronic Lymphocytic Leukemia Research
- Click Chemistry and Applications
- Neuroendocrine Tumor Research Advances
- Immunodeficiency and Autoimmune Disorders
- Hematopoietic Stem Cell Transplantation
Walter and Eliza Hall Institute of Medical Research
2012-2024
The University of Melbourne
2012-2022
BRCA1 -mutated tumors may be particularly vulnerable to dual checkpoint inhibition.
Synthetic CpG oligonucleotides (ODN) have potent immunostimulatory properties exploited in clinical vaccine trials. How ODN are captured and delivered to the intracellular receptor TLR9, however, has been elusive. Here we show that DEC-205, a multilectin expressed by variety of cells, is for ODN. When used as an adjuvant, mice deficient DEC-205 impaired dendritic cell (DC) B-cell maturation, unable make some cytokines such IL-12, display suboptimal cytotoxic T-cell responses. We reveal...
Abstract Venetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using phase Ib 3 + dose-escalation expansion study design, 33 patients ER BCL2-positive metastatic disease (mean prior regimens, 2; range, 0–8) were treated daily tamoxifen (20 mg) venetoclax (200–800 mg). Apart from uncomplicated “on-target” lymphopenia, no dose-limiting toxicities or high-grade adverse events observed the escalation (15...
Abstract Purpose: Although cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly extend tumor response in patients with metastatic estrogen receptor–positive (ER+) breast cancer, relapse is almost inevitable. This may, part, reflect the failure of CDK4/6 to induce apoptotic cell death. We therefore evaluated combination therapy ABT-199 (venetoclax), a potent selective BCL2 inhibitor. Experimental Design: family member expression was assessed following treatment endocrine...
One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on PRMT5 cancer cells with MTAP deletion. We report discovery clinical stage MTA-cooperative inhibitor AMG 193, which preferentially binds presence MTA and potent biochemical cellular activity MTAP-deleted across lineages. In vitro, inhibition induces DNA damage, cell cycle arrest, aberrant alternative mRNA splicing cells. human line patient-derived xenograft models, 193...
Abstract The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role adaptive unclear. Here we show that the LUBAC components HOIP, HOIL-1 SHARPIN have roles late thymocyte differentiation, FOXP3 + regulatory T (Treg)-cell development Treg cell homeostasis. activity not required to prevent TNF-induced apoptosis or necroptosis but necessary transcriptional programme of penultimate stage differentiation. cell-specific ablation HOIP...
<p>Supplementary Methods: SDMA Imaging Assay, ELISA, Immunohistochemistry</p>
<p>Supplementary Figure S6. AM-9747 treatment results in increased DNA damage and cellular senescence BxPC-3 cells</p>
<p>Supplementary Figure S8. AMG 193 treatment in BxPC-3 tumors does not affect circulating blood cells</p>
<p>Supplementary Figure S5. <i>In vitro</i> target validation, RNA-seq, and additional cell cycle data in WT MTAP-deleted tumor cells</p>
<p>Supplementary Figure S2. SPR AMG 193 competitive chaser experiment</p>
<p>Supplementary Figure S3. HCT116 isogenic pair validation</p>
<p>Supplementary Figure S1. SPR chaser characterization</p>
<p>Supplementary Figure S7. Time course SDMA analysis, CDX models versus AMG 193, and AM-9747 PDX trial</p>
<p>Supplementary Figure S10. AMG 193 and sotorasib combination is synergistic in the MIAPACA2 MTAP–deleted, KRAS G12C mutant cell line</p>
<p>Supplementary Figure S9. AMG 193 chemotherapy combinations are synergistic in the H292 MTAP-deleted NSCLC cell line</p>
<div>Abstract<p>One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on protein arginine methyltransferase 5 (PRMT5) cancer cells with <i>MTAP</i> deletion. We report discovery clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds presence MTA and potent biochemical cellular activity MTAP-deleted across lineages. <i>In vitro</i>, inhibition induces DNA damage,...