Abstract 2288P
Background
Current therapies for oncology patients are often ineffective and present severe side effects, decreasing the quality of life of patients significantly. Recent advances in technology and biomedical research have contributed to the characterization of the the human microbiome and uncovered its important role in health and disease. Those findings allowed monitoring, preventing or even curing human disease through specific microbiome interventions. In this context, we now provide a novel and unique solution for the treatment of solid tumors.
Methods
C57BL/6 and BALB/c mice were used to perform the in vivo studies. MC-38, CT-26, B16, LLC1.1 and 4T1 cells were used for the heterotopic tumor injections. Flow cytometry and histological analysis were performed to analyze the immune cell compartments. Metagenomics analysis and whole genome sequence were performed to identify the bacterial strains. Metabolomics analysis were conducted to analyse the serum composition of mice and humans.
Results
Based on human CRC data, we identified specific bacteria that are less abundant in CRC patients compared to healthy individuals. When these bacteria are applied in mice, they show very high efficacy as a monotherapy in tumor models for CRC, melanoma, breast and lung cancer through specific activation of CD8+ T-cells ( Montalban-Arques et al. 2021 ). Based on this finding, we now identified the bacterial metabolite that is responsible for the observed immune-activating effect as well as the receptor that is targeted by that molecule, providing a defined mode of action. This allows us to better evaluate our pre-clinical safety and efficacy studies and it give us a strong advantage, comparing to the current microbiome-based solutions where mechanisms remain unkown.
Conclusions
With our promising proof of concept studies, we are aiming to develop a safe and novel microbiome-based solution for the treatment of solid tumors. The specific bacterial strains will be applied to cancer patients in lyophilized form contained in gastro resistant capsules with colonic release. Our bacteria-based cancer therapy aims to improve treatment efficacy while reducing side effects and increasing the life expectancy and quality-of-life of cancer patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Recolony AG.
Disclosure
E. Katkeviciute, P. Busenhart, A. Montalban-Arques: Financial Interests, Personal and Institutional, Stocks or ownership: Recolony AG.
Resources from the same session
2252P - KRAS G12C inhibition using MRTX849: A novel radio-sensitizing partner
Presenter: Marina Milic
Session: Poster session 08
2253P - RAS-precision medicine trans-atlantic partnership: Comparative analysis of KRAS codon 12 and 13 mutations in non-small cell lung cancer
Presenter: Helen Adderley
Session: Poster session 08
2254P - Persisting RAS addiction: A therapeutic vulnerability in the context of KRAS G12C inhibitor resistance
Presenter: George Morrissey
Session: Poster session 08
2255P - Clinicogenomic landscapes and hallmarks of KRAS amplification in human cancers
Presenter: Biagio Ricciuti
Session: Poster session 08
2256P - The microenvironment of normal mucosa could predict recurrence in the stage II/III colorectal cancer: Multicenter, multiomics study
Presenter: Yeonghak Bang
Session: Poster session 08
2257P - Stereotactic body radiation therapy and atezolizumab combination: Results of the international multi-centre SABR-PDL1 phase II trial colorectal cohort
Presenter: Antonin Levy
Session: Poster session 08
2258P - Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: Drug screen optimization and correlation with patient response
Presenter: Lidwien Smabers
Session: Poster session 08
2259P - An artificial neural network system to predict the fraction of type I polarized macrophage
Presenter: Tongji Xie
Session: Poster session 08
2260P - Berberine associated to SGLT-2i exerts synergistic cardioprotective effects in cardiac cells exposed to the HER2-blocking agent trastuzumab through pAMPK activation and reduction in Interleukin-6 levels
Presenter: Andrea Paccone
Session: Poster session 08
2261P - A head-to-head comparison for detecting PIK3CA mutations in circulating tumor DNA of advanced HR+/HER2- breast cancer patients
Presenter: Nadia Dandachi
Session: Poster session 08