Abstract 2271P
Background
An abundance of cancer associated fibroblasts (CAFs) in stromal rich tumours is a barrier to the effectiveness of anticancer therapies. We have developed an oncolytic adenovirus - THEO-260 - that is capable of lysing both cancer cells and CAFs in ovarian patient tumours ex vivo. Here, we present data to support the progression of THEO-260 to first in human (FIH) clinical trials.
Methods
THEO-260 efficacy was assessed in cell lines, multicellular spheroids, ex vivo fresh ovarian patient samples and mouse models bearing human cancers and stromal CAFs. The safety was assessed in primary human normal cells and in immunocompetent mice.
Results
THEO-260 killed a panel of cell lines from ovarian cancer (n=8), in addition to different stromal rich tumour types (pancreatic, colorectal, lung, and breast cancer; n=9) and multicellular spheroids. Moreover, THEO-260 was highly efficacious in fresh ovarian patient materials, killing cancer cells and CAFs in ascites and tumour samples (n=24). THEO-260 outperforms SOC chemotherapies including paclitaxel and PARP inhibitors. In vivo, THEO-260 shows antitumor efficacy, with a complete reduction in tumour volume and is superior to SOC in the platinum resistant ovarian cancer model with human CAFs (COV318+MRC5). THEO-260 also prevents ovarian intraperitoneal metastasis formation in vivo in a human ovarian adenocarcinoma model with CAFs (SKOV3+MRC5). As expected THEO-260 does not replicate in non-human primary cells, supporting replication selectivity testing in normal human primary cells rather than in animal models. THEO-260 demonstrates high selectivity for tumours, with negligible levels of replication and production of infectious virions in all normal primary human cells tested. THEO-260 was also shown to be safe in vivo in immunocompetent mouse models, when tested at repeated and escalating, clinically relevant, dose levels. The genetic and temperature stability of THEO-260 has been confirmed and is currently being GMP manufactured to high yields.
Conclusions
Our data confirms that THEO-260 is efficacious and safe, supporting the initiation of FIH clinical trials in high grade serous ovarian cancer patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Theolytics Ltd.
Funding
Theolytics Ltd.
Disclosure
M. Bazan Peregrino, S.C. Frost, C. Negroni, C. Moriconi, T. Perry, W. Taverner, B. Nicholls, D. Saunders, R. Ackerman-Johnson, A. Lim: Financial Interests, Institutional, Full or part-time Employment: Theolytics Ltd. K. Fisher, M.R. Duffy: Financial Interests, Institutional, Stocks or ownership: Theolytics Ltd. All other authors have declared no conflicts of interest.
Resources from the same session
2262P - Baseline-informed versus tumor-agnostic minimal residual disease (MRD) concordance study in patients with HER2+ gastroesophageal adenocarcinoma patients
Presenter: Pan Du
Session: Poster session 08
2263P - Ethnicity-specific distribution of BRCA1, BRCA2, PALB2 and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus
Presenter: Evgeny Imyanitov
Session: Poster session 08
2264P - Proteomics-based phenotypic classification of non-smallcell lung cancer
Presenter: Olena Berkovska
Session: Poster session 08
2265P - miR-4487 enhances gefitinib-mediated ubiquitination and autophagic degradation of EGFR in non-small cell lung cancer cells by targeting USP37
Presenter: Sei-Hoon Yang
Session: Poster session 08
2266P - IMMUcan consortium: Focus on the first results of the non-small cell lung cancer (NSCLC) cohort
Presenter: Marie Morfouace
Session: Poster session 08
2267P - Coronary heart disease and risk of lung cancer: A two-sample Mendelian randomization study
Presenter: Cai Chen Li
Session: Poster session 08
2269P - Patient derived xenografts generated from circulating cancer stem cells on chorioallantoic membrane as an alternative pre-clinical model for personalized medicine in pancreatic cancer
Presenter: Monika Pizon
Session: Poster session 08
2270P - Integrative analyses of bulk and single-cell RNA-seq identified diabetes mellitus-related signature as a prognostic factor in pancreatic adenocarcinoma
Presenter: Le Tang
Session: Poster session 08
2272P - Minimal DNA-methylation (DNAm) signatures for non-invasive tumor-agnostic estimation of tumor content (TC) and molecular subtype in patients (pts) with metastatic breast cancer (mBC)
Presenter: Matteo Benelli
Session: Poster session 08
2273P - Influence of body mass index (BMI) on the response to chemotherapy in patients with HER2+ breast cancer: Role of the leptin axis
Presenter: Marta González Rodríguez
Session: Poster session 08