Helen L. Lowe
A5067711058- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Lung Cancer Treatments and Mutations
- Neuroendocrine Tumor Research Advances
- Neuroblastoma Research and Treatments
- Lung Cancer Research Studies
- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- Acute Lymphoblastic Leukemia research
- Immunotherapy and Immune Responses
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Cells and Metastasis
- Biosimilars and Bioanalytical Methods
- Renal cell carcinoma treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Lymphoma Diagnosis and Treatment
- COVID-19 epidemiological studies
- Colorectal Cancer Treatments and Studies
- Cancer-related molecular mechanisms research
London Cancer
2014-2025
University College London
2015-2025
CRUK Lung Cancer Centre of Excellence
2012-2023
Cancer Institute (WIA)
2016-2023
University College London Hospitals NHS Foundation Trust
2021-2022
Monash Health
2020
Monash University
2020
University College Hospital
2016
Cancer Research UK
2007
The Royal Free Hospital
2005
Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and genome evolution have been limited to small retrospective cohorts. We wanted prospectively investigate in relation clinical outcome determine the clonal nature of driver events evolutionary processes early-stage NSCLC.
Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, polymorphic nature locus has precluded accurate HLA copy-number analysis. Here, we heterozygosity in (LOHHLA), computational tool determine allele-specific copy number from sequencing data. Using LOHHLA, find that LOH occurs 40% non-small-cell lung cancers (NSCLCs) and associated with high subclonal neoantigen burden,...
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that expression largely restricted to tumor-infiltrating Treg in mice humans. While existing were observed deplete the periphery, upregulation of inhibitory Fc gamma receptor (FcγR) IIb tumor site prevented intra-tumoral cell depletion, which may underlie lack...
Abstract Recognition and elimination of pathogens cancer cells depend on the adaptive immune system. Thus, accurate quantification subsets is vital for precision medicine. We present lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell B fractions, class switching clonotype diversity whole-genome data at depths as low 5× coverage. By applying ImmuneLENS to 100,000 Genomes Project, we identify genes enriched with somatic mutations in cell-rich tumors,...
Abstract We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels MM41 are rapidly transported into cell nuclei and were found to accumulate tumour. is quadruplex-interactive compound which...
Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with fast off rate, designed more physiologic T-cell activation to reduce toxicity improve engraftment. describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) B-ALL.Patients age ≥ 16...
To investigate posttreatment circulating tumor cell (CTC) counts in patients with neuroendocrine neoplasms (NENs) as a predictive biomarker for disease progression and overall survival (OS).
Antibody-directed enzyme prodrug therapy (ADEPT) requires highly selective antibody-mediated delivery of to tumor. MFE-CP, a multifunctional genetic fusion protein antibody and enzyme, was designed achieve this by two mechanisms. First using high affinity specificity single chain Fv directed carcinoembryonic antigen. Second rapid removal antibody-enzyme from normal tissues virtue post-translational mannosylation. The purpose paper is investigate these dual functions in an animal model...
Neuroendocrine tumours (NET) overexpress somatostatin receptors (SSTR) that can be targeted for therapy. Somatostatin receptor expression is routinely measured by molecular imaging but the resolution insufficient to define heterogeneity. We hypothesised SSTR could on circulating tumour cells (CTCs) and used investigate heterogeneity of track changes during
Bone metastases are associated with a worse outcome in patients neuroendocrine tumours (NETs). Tumour overexpression of C-X-C chemokine receptor 4 (CXCR4) appears predictive skeletal involvement. We investigated the role circulating tumour cells (CTCs) and CXCR4 expression on CTCs as potential predictors skeleton invasion.Blood from metastatic bronchial, midgut or pancreatic NET (pNET) was analysed by CellSearch. immunohistochemistry performed matched formalin-fixed paraffin-embedded (FFPE)...
Abstract Human tumors are diverse in their natural history and response to treatment, which part results from genetic transcriptomic heterogeneity. In clinical practice, single-site needle biopsies used sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution the sampling bias problem analyzing multiregion whole-exome RNA sequencing data for 450 tumor regions 184 patients...
This is a feasibility study to determine whether circulating tumour cells (CTCs) are detectable and suitable for molecular profiling in advanced endometrial cancer (aEC).Between October 2012 February 2014, 30 patients with aEC had baseline up 3 follow-up samples. CTCs stathmin expression were evaluated using the CellSearch platform. Epithelial cell adhesion molecule (EpCAM) immunohistochemistry performed on FFPE tissue.Eighteen from (60%) during [1 CTC (n = 7), 2 4), 1), 4 2), 7 8 22 172 1)...
Abstract Background DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) solid tumours (ovarian cancer) that clinical sensitivity to such can result from a defect ICL processing leading their persistence. Conversely, enhanced repair acquired resistance following chemotherapy. The of ICLs is complex but it assumed the ‘unhooking’ step...
Abstract Background Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and accurate prognostic markers although the optimum threshold has not been defined. Objective This work aims to define optimal CTC thresholds PanNET midgut NETs. Patients Methods CellSearch was used enumerate CTCs 199 metastatic pancreatic (PanNET) (90) or NETs (109). were followed for progression-free survival (PFS) overall (OS) a minimum of 3 years until death. Results The area...
ABSTRACT Aim: To investigate the content and face validity of a patient-reported outcome measure used by Australian physiotherapists in assessment inflammatory conditions lactating breast. Methods: Sixty one experts representing ‘women who previously had breast’ (48%), ‘clinicians’ (38%) ‘academics’ (8%) interested women's health 7% unidentified participants were invited to complete three round Delphi study. Results: Ninety five percent agreed that overall, was appropriate for use assessing...
In this study, we set out to establish whether fludarabine could enhance the DNA interstrand crosslinking capacity of SJG-136 in primary human chronic lymphocytic leukaemia (CLL) cells and thereby offer a rationale for its clinical use combination with SJG-136. rapidly induced CLL which was concentration-dependent. Further, level correlated sensitivity SJG-136-induced apoptosis (P=0.001) higher levels were by (P=0.002). All samples tested (n=40) demonstrated synergy between (mean index...
Abstract Background Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC). Methods Treatment-naive patients received 4-day pulses AZD8931 irinotecan/5-FU (FOLFIRI) single-arm trial. Primary endpoint for I was dose limiting (DLT); II best overall...
Single-cell profiling of circulating tumor cells (CTCs) as part a minimally invasive liquid biopsy presents an opportunity to characterize and monitor heterogeneity evolution in individual patients. In this study, we aimed compare single-cell copy number variation (CNV) data with tissue define the degree intra- inter-patient genomic heterogeneity. We performed next-generation sequencing (NGS) whole-genome CNV analysis 125 single CTCs derived from seven patients neuroendocrine neoplasms (NEN)...