Imperial College London
Portrait Picture

DrJonathanKrell

Faculty of Medicine, Department of Surgery & Cancer

Clinical SL in Medical Oncology (Gynaecological Oncology)
 
 
 
//

Contact

 

j.krell

 
 
//

Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Lythgoe:2021:10.1016/j.annonc.2021.08.1065,
author = {Lythgoe, M and Adriani, M and Stebbing, J and Clark, J and Pickford, E and Frampton, A and Liu, D and Kyrgiou, M and Rees, E and Fyvie, G and Stevenson, A and Krell, J},
doi = {10.1016/j.annonc.2021.08.1065},
journal = {Annals of Oncology},
pages = {S607--S607},
title = {543P Neoadjuvant MRx0518 treatment is associated with significant gene and metagene signature changes in solid tumours},
url = {http://dx.doi.org/10.1016/j.annonc.2021.08.1065},
volume = {32},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundMRx0518 is an oral live biotherapeutic with potent immunostimulatory activity and anti-tumorigenic efficacy in murine models of lung (LLC1), kidney (Renca) and breast (EMT6) cancer. Previous reports have demonstrated a favourable safety profile in neoadjuvant and metastatic clinical settings, with emerging evidence of immune modulation. We performed a comprehensive analysis of the gene and metagene signature in cancer patients treated with MRx0518 monotherapy.MethodsTreatment-naïve patients with a histologically confirmed diagnosis of cancer scheduled for surgical resection were recruited from April 2019 to February 2020. Patients received 1 capsule of MRx0518 (1x1010 to 1x1011CFU) twice daily from inclusion until the day preceding surgery. Safety and tolerability (CTCAE v4.03) were the primary endpoints of this study. Comprehensive biomarker analysis was also performed in paired pre-treatment (diagnostic biopsy) and post-treatment (surgical specimen) samples using the NanoString IO 360 panel to explore gene and metagene signatures.Results31 samples were collected across tumour groups including breast (n=13) prostate (n=8), uterine (n=6), melanoma (n=2) and bladder (n=2). Differential expression analysis showed significant (p<0.05) increases in genes and metagenes associated with anti-tumour activity, including antigen presentation (AXL & CXCL12), innate immune processes (CHUK, RELA, PPARG & HRAS), interferon response (IFNGR1 & IFNGR2), Th1 cells and CD8+ cells following MRx0518 therapy, echoing preclinical findings. Novel changes, not previously detected in murine models, involving endothelial, mast cells, inflammatory myeloid and inflammatory chemokines were also observed, suggesting MRx0518 may have additional in vivo anti-tumorigenic effects. These changes were more pronounced in the breast cancer cohort.ConclusionsThis analysis, mirrors previous immunostimulatory activity and anti-tumorigenic efficacy observations seen in pre-clini
AU  - Lythgoe,M
AU  - Adriani,M
AU  - Stebbing,J
AU  - Clark,J
AU  - Pickford,E
AU  - Frampton,A
AU  - Liu,D
AU  - Kyrgiou,M
AU  - Rees,E
AU  - Fyvie,G
AU  - Stevenson,A
AU  - Krell,J
DO  - 10.1016/j.annonc.2021.08.1065
EP  - 607
PY  - 2021///
SN  - 0923-7534
SP  - 607
TI  - 543P Neoadjuvant MRx0518 treatment is associated with significant gene and metagene signature changes in solid tumours
T2  - Annals of Oncology
UR  - http://dx.doi.org/10.1016/j.annonc.2021.08.1065
UR  - https://www.sciencedirect.com/science/article/pii/S0923753421032944?via%3Dihub
UR  - http://hdl.handle.net/10044/1/91877
VL  - 32
ER  -
Download