An Application to Immuno-Oncology: our first webinar from our new lab in Boston
Webinar on Immuno-Oncology by Rima AIT-BELKACEM, PhD
December 12 | 2 pm East Coast Time/ 11 am West Coast Time | Online
In this webinar you will discover our brand new facility, our Lab Manager David Calligaris, PhD, and its expertise in oncology but also our technique applied to oncology based on the subsequent example described by Rima Ait-Belkacem, PhD.
To register please click HERE.
Quantitative Mass Spectrometry Imaging Applied to Study Immunotherapies:
Target Exposure, Engagement and Infiltration of Active Immune Cells into Tumor Microenvironment
Cancer immunotherapy englobes treatments that harness and enhance the innate powers of the patient’s immune system to fight cancer. Indoleamine 2,3-dioxygenase 1 (IDO-1) has been one of the first targets that has really been purposed for immuno-oncology applications. IDO-1 is an intracellular immune checkpoint protein that catalyzes the breakdown of the essential amino acid tryptophan (Trp). Dysregulation of this enzyme can result in the suppression of an appropriate immune response. Inhibition of IDO-1 has been shown to reinvigorate the natural immune response to cancer cells. The promoted infiltration of active immune cells into the tumor microenvironment is an important feature of many immunotherapies. Unlike in vitro (enzymatic kits) and ex vivo (LC-MS/MS and microdialysis) analysis.
Quantitative Mass Spectrometry Imaging (QMSI) analysis combined to immunostaining could allow both target exposure and engagement studies as a basis of a true on tissue PK/PD analysis. Basically, MSI is able to simultaneously record the distribution of thousands of biomolecules directly from tissue, without labeling and without prior knowledge. MSI based on matrix-assisted laser desorption/ionization (MALDI) applied with different tissue preparation procedures can be used to analyze proteins, peptides, glycans, lipids, metabolites, and drugs. Carrying forward, looking to histological localization, interaction and quantification of metabolites and nutrients are high of importance for microenvironment tumor metabolic interactions understanding.
In this webinar, we will present the latest development to monitor distribution and absolute quantification of Trp and its principal metabolite (Kynurenine, Kyn) by high-resolution MALDI imaging (Solarix 7T, Bruker Daltonics) in P815 and CT26 tumor murine models. High definition overlays between the IDO1 enzyme and its Kyn product, as well as an analytical confirmation using LC-MS/MS analysis in plasma and blood samples were performed. Finally, this proof-of-concept study highlighted the metabolic signatures as myeloid and glycolysis markers translating many immune consequences due to the modulated IDO1 expression levels:
- Inhibition of T cell effector function and metabolism,
- Activation of regulatory T cell function/differentiation
- Generation of tolerogenic Dendritic Cells
- Promotion of M2-Macrophages…
Keywords: Mass spectrometry imaging, Computer vision, Data analysis, Quantitative analysis, Morphology
About Dr. Ait-Belkacem, R&D Manager
After having obtained her Master degree in Oncology Science and Oncopharmacology, a PhD in Oncology and Imaging Mass Spectrometry applied to Glioblastoma cancer; and a Post-Doc in Cancer Biology and Proteomics, Dr. Ait-Belkacem, R&D Manager, has the ambition to develop the oncology research field at ImaBiotech. Currently, her team is mainly leading the way in Immuno-Oncology (I-O) research.
ImaBiotech supports pharmaceutical industry with innovative Imaging services that predict more accurately which treatment will work in stratified population.
ImaBiotech is a Contract Research Organization (CRO) with two facilities one in Boston (MA) and one in France. The company offers innovative services to the pharmaceutical research to provide better drug efficacy and toxicity evaluations from preclinical to clinical stages, making better and safer drugs.
Services are based on different imaging techniques combined to Quantitative Mass Spectrometry a technology developed and constantly improved by ImaBiotech. Quantitative Mass Spectrometry (QMSI) has been developed for decades and allows to detect elements and molecules without labelling. ImaBiotech has developed the quantitative aspects through many patents making ImaBiotech the worldwide leader in this field. QMSI is a game changer of the pharmaceutical industry in all therapeutic areas. While actual techniques provide global information, this molecular technique brings deeper information about drug localization and its pharmacology effects to recover disease tissues and damaged cells. This increases the interpretation of drug efficacy and toxicity improving drugs and improving time to market. To interpret datas we’ve developed, thanks to our patents, two softwares called Quantinetix and Multimaging to interpret pharmacology in tissue.