Cancer Immunotherapy. The hope and the risk
The development of immunotherapies, specially check point inhibitors (CPIs), has been one of the key achievements in recent times in our fight against cancer. In melanoma, CPIs have unprecedented response rates in up 60% of patients when anti-CTLA-4 anti-PD-1 therapies are combined. One can consider CPIs the actual 21st century cancer therapy.
However, this effectiveness comes with a price. A large part of the patients treated with CPIs suffered severe autoimmune side effects in vital body organs. This includes lungs, bowel, joints and muscles, including heart.
However, this effectiveness comes with a price. A large part of the patients treated with CPIs suffered severe autoimmune side effects in vital body organs. This includes lungs, bowel, joints and muscles, including heart.
Source: modified from Mikael Häggström, via Wikimedia https://commons.wikimedia.org/wiki/File:Internal_organs.png
-Omics era profiling of patient samples to counterattack CPIs-induced autoimmunity
In MelAutim our aim is to improve our understanding of the molecular and cellular mechanisms underlying the interplay between autoimmunity and cancer immunotherapy. To this end, we profile patient samples with cutting-edge technologies for molecular profiling like DNA/RNA-Seq, transcriptomics and proteomics.
However, the amount of data generated and the complexity of the molecular and cellular mechanisms investigated pose a threat to our ability to understand.
However, the amount of data generated and the complexity of the molecular and cellular mechanisms investigated pose a threat to our ability to understand.
We profile molecularly blood and tissue samples from patient suffering CPIs-induced autoimmunity
Source: modified from Jonathan Bailey, NHGRI, via Wikimedia https://commons.wikimedia.org/wiki/File:Nanopore_Sequencing_(27820412495).jpg
Computational modelling and artificial intelligence. Our golden weapon
To make possible the understanding of the data, in MelAutim we utilize computational modelling and artificial intelligence to reconstruct and simulate the molecular and cellular networks behind the CPIs-induced autoimmunity. Our aim is to detect molecular signatures characterizing distinct groups of patients suffering the side effects.
We envision that this knowledge will help us designing personalized coadjuvant therapy to mitigate the autoimmune side effects of CPIs.
We envision that this knowledge will help us designing personalized coadjuvant therapy to mitigate the autoimmune side effects of CPIs.
Simulation of a multi-level computational model of melanoma micrometastasis under CPI therapy as conceived in MelAutim
This project is funded by the German Ministry of Research and Education (BMBF) under the e:Med program
