A5013988479- RNA modifications and cancer
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Immunotherapy and Biomarkers
- Folate and B Vitamins Research
- Immunotherapy and Immune Responses
- RNA Research and Splicing
- CAR-T cell therapy research
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Drug Transport and Resistance Mechanisms
- Radiopharmaceutical Chemistry and Applications
- interferon and immune responses
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic and Hepatic Oncology Research
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- PARP inhibition in cancer therapy
- Esophageal Cancer Research and Treatment
- Chronic Myeloid Leukemia Treatments
- Fibroblast Growth Factor Research
- Brain Metastases and Treatment
- Advanced Breast Cancer Therapies
- Cancer, Hypoxia, and Metabolism
Cancer Council SA
2021-2024
King's College London
2018-2023
Kings Health Partners
2023
St Thomas' Hospital
2023
Guy's and St Thomas' NHS Foundation Trust
2018-2023
Royal Darwin Hospital
2017-2021
Guy's Hospital
2018
PURPOSE For patients with metastatic hormone-sensitive prostate cancer (mHSPC), delaying progression to castration-resistant disease is important not only for overall survival (OS) but also patients' quality of life. Darolutamide plus androgen-deprivation therapy (ADT) docetaxel improved OS versus ADT and in mHSPC. The ARANOTE trial evaluated darolutamide without chemotherapy METHODS In this global phase III trial, were randomly assigned 2:1 receive 600 mg twice daily or placebo, concomitant...
Abstract Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions multiple oncogenic processes. MTL-CEBPA is first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. Patients Methods: We conducted phase I, open-label, dose-escalation trial in adults with advanced hepatocellular carcinoma (HCC) cirrhosis, or resulting from nonalcoholic steatohepatitis liver metastases. received...
Abstract All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers potential enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with primary objective exploring safety and tolerability MOv18 chimeric first-in-class IgE antibody, in patients tumours expressing relevant antigen, folate receptor-alpha. The incorporated skin prick basophil activation tests (BAT) to select at...
Transplant patients were excluded from the pivotal phase III trials of checkpoint inhibitors in metastatic melanoma. The efficacy and toxicity profiles this cohort are not well described. To best our knowledge, is first case report a renal transplant patient with stage IV melanoma treated programmed cell death protein 1 inhibitor that led to both treatment failure graft rejection.We present 58-year-old white man long-standing cadaveric who was diagnosed B-Raf Proto-Oncogene, Serine/Threonine...
BACKGROUNDPhase 1 study of ATRinhibition alone or with radiation therapy (PATRIOT) was a first-in-human phase I the oral ATR (ataxia telangiectasia and Rad3-related) inhibitor ceralasertib (AZD6738) in advanced solid tumors.METHODSThe primary objective safety. Secondary objectives included assessment antitumor responses pharmacokinetic (PK) pharmacodynamic (PD) studies. Sixty-seven patients received 20-240 mg BD continuously intermittently (14 28-day cycle).RESULTSIntermittent dosing better...
Abstract Background: Commercially available CTLA-4 antibodies are associated with a high incidence of immune mediated adverse events. Evalstotug (BA3071) is conditionally active biologic (CAB) anti–CTLA-4 monoclonal antibody that blocks the interaction its ligands in low-pH conditions tumor microenvironment. CABs not masked or caged and do require enzymatic cleavage for activation. They reversibly bound acidic microenvironment, which expected to reduce off-tumor immune-related events,...
The presence of inhibitory immune cells and difficulty in generating activated effector T remain obstacles to development effective cancer vaccines. We designed a vaccine regimen combining human telomerase reverse transcriptase (hTERT) peptides with concomitant therapies targeting regulatory (Tregs) cyclooxygenase-2 (COX2)-mediated immunosuppression. This Phase 1 trial combined an hTERT-derived 7-peptide library, selected ensure presentation by both HLA class-I class-II 90% patients, oral...
2601 Background: TransCon IL-2 β/γ (TC-IL2 β/γ) is a novel prodrug with sustained release of an IL-2Rβ/γ-selective analog (IL-2 β/γ). transiently attached to inert carrier by linker, which under physiological conditions, releases active in predictable manner. This results lower Cmax and longer half-life, expected widen the therapeutic index. Methods: Dose escalation TC-IL2 IV as monotherapy (mono) or combination pembrolizumab (P) evaluated doses starting at 20 µg/kg every 3 weeks. Cohort 4...
Abstract Background Paraneoplastic neurological syndrome is an immune-mediated phenomenon where antibodies from tumor cells are produced against neuronal proteins. Amphiphysin antibody onconeural linked to the diagnosis of breast cancer and small-cell lung cancer. It uncommon typically associated with stiff-person syndrome, which 90% patients eventually diagnosed Case presentation We present a case 47-year-old Caucasian woman metastatic hormone receptor-positive who developed bilateral...
2546 Background: SUPLEXA therapeutic cells are the initial autologous and non-engineered candidate to emerge from novel ENLIST training platform. Manufacturing is robust, reproducible with an acceptable cost of goods. The method requires 35 days produce multiple doses. Multiple mechanisms have been delineated all appear complement that immune checkpoint inhibitors (ICIs) serving enhance number primed anti-tumor host T while ICIs serve increase durability by blocking their premature...
11555 Background: Shasqi is a clinical stage biotech that uses click chemistry, Nobel Prize winning technology, to selectively activate cancer treatments at the tumor. The Click Activated Protodrugs Against Cancer (CAPAC) platform comprises of 1) tumor targeting agents, which carry an activator, and 2) attenuated drugs, are activated by agent through maximizing therapeutic index minimizing toxicities. We have demonstrated proof concept with SQ3370, intratumorally injected SQL70 biopolymer...
2602 Background: Immune checkpoint inhibition of cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) in combination with programmed cell death 1 (PD-1) has demonstrated durable clinical benefit patients advanced solid tumors. However, dose density is limited due to toxicity. BA3071 a conditionally active biologic (CAB) anti–CTLA-4 monoclonal antibody that blocks the interaction CTLA-4 its ligands CD80 and CD86 [1]. CABs are activated within acidic tumor microenvironment. Conditional...
<h3>Background</h3> SUPLEXA cells are individualized cancer therapeutic generated from patients' PBMCs using a novel immune training approach driven by engineered immunomodulatory tumor called ENLIST cells. acquire potent cytolytic activity, antigen presenting cell capacity, and properties. Results of first-in-human clinical trial for therapy has been completed, achieving all prespecified endpoints. This report provides the results transcriptional proteomic profiling as well their remarkable...
<h3>Background</h3> SUPLEXA therapeutic cells are the initial autologous and non-engineered candidate to emerge from novel ENLIST training platform. Manufacturing is robust, reproducible with an acceptable cost of goods. The vein time this method 35 days yields multiple doses. Characterization have identified proteins involved in known anti-tumor mechanisms ranging direct tumor cytolysis antigen presentation function. These, appear complement that immune checkpoint inhibitors (ICIs) by...
<h3>Background</h3> Currently, toxicity limits dose density of CTLA-4 inhibitor + PD-1 therapy in patients (pts) with advanced solid tumors.<sup>1–3</sup> Evalstotug (BA3071) is a conditionally active biologic (CAB) anti–CTLA-4 monoclonal antibody that blocks the interaction its ligands low-pH conditions tumor microenvironment.<sup>4</sup> CABs are reversibly bound acidic microenvironment, which reduces off-tumor immune-related adverse events, enhances host immunity, avoids tissue-mediated...
<h3>Background</h3> SUPLEXA is a first-in-class, autologous, adoptive immunotherapy; prepared from patients' PBMCs that contains cytolytic populations of NK cells, NKT-like, gd T and ab CD8/CD4 cells. <h3>Methods</h3> This FIH Phase 1, non-comparative, open-label, basket-design study NCT05237206. The has enrolled 28 patients in Australia with histologically or cytologically radiographically confirmed cancer for whom standard care have failed. All received the minimum dosing regimen 2.5...
3085 Background: SQ3370, a novel therapy, utilizes Shasqi’s proprietary Click Activated Protodrugs Against Cancer (CAPAC) platform where mutually-reactive click chemistry groups release Doxorubicin (Dox) at the tumor site minimizing systemic exposure. In animals, SQ3370 enhanced survival, T-cell infiltration and antitumor responses in injected non-injected tumors. Minimal to no toxicity, including cardiotoxicity was seen up 9-fold dose increases animals. Conventional Dox can induce...
<p>Supplementary Legends</p>
<p>Trial Protocol</p>
<p>qPCR of CEBPA mRNA levels at days 2, 8 and 15 following treatment</p>
<p>Showing complete radiological response of lung metastases</p>
<p>A) CT and MRI of patient with prolonged partial response MTL-CEBPA treatment B) IFN-gamma, NFkB IL6 trend at days 1, 8 15 following C) AFP change from baseline to 4, 16 weeks on treatment</p>