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.
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