Advantages
- Detects complex interactions and proximity information (multifactorial interactions) among multiple proteins from a little clinical tissue.
- Enable to analyzes spatial interactions from clinical tissue, providing more in vivo-like information.
Technology Overview & Background
The tumor microenvironment comprises various cells, including cancer cells, immune cells, and fibroblasts. Tumor dynamics are regulated by complex interactions among these cells, ligands, and various intracellular proteins. Despite the development of numerous immunotherapeutic agents and molecular-targeted drugs expanding therapeutic options, patient responses to treatment vary, with some agents showing effective in certain patients but not others. Predicting therapeutic responsiveness among many drugs with high accuracy and selecting the optimal therapy is ideal, but such methods are scarce. Traditionally, protein-protein interactions have been analyzed using biochemical methods based on immunoprecipitation, which require large specimen amounts and cannot easily analyze spatially segmented protein-protein interactions.
In response to this challenge, researcher have developed the IBMseq (Interaction Between Molecules seq) for analyzing interactions between multiple proteins. In this method, PCR is performed in a hydrogel polymer using an antibody labeled with a DNA barcode to identify each molecule and multiple primers (UEIs) incorporating random sequences to distinguish PCR reactions. The primers are bound to the polymer, and the PCR product has a network structure consisting of the DNA barcode and each UEI that retains spatial information. Next-generation sequencing can then be used to count the number of bindings between each UEI and antibody molecule. It enable to analyze multifactorial interactions. The IBMseq method is expected to be used for quantitative and spatial analysis of multifactor interactions not only inside and outside cells, but also in tissues.
Patent
Principal Investigator & Academic Institution
Prof. Keisuke NIMURA (Initiative for Advanced Research, Gunma University)
Development Stages & Plans
- We have confirmed that multifactor interactions can be detected on the plasma membrane and in the nucleus of B cells. The interaction between three molecules and its changes over time have also been observed.
- In renal cancer tissue, interactions between PD-1 and PD-L1, and between HLA and HLA, among others, have been confirmed using IBMseq.
- We are testing the feasibility of applying this method to analyze interactions between various immune checkpoint factors, cell surface markers, and transcription factors in tumor tissues.
- We are exploring its applicability in determining responses to immune checkpoint inhibitors and prognoses.
Expectations
TECH MANAGE CORP. is looking for a diagnostic company/start-up that is interested in this invention for commercialization. We can also arrange a meeting with the PI of this invention. Please feel free to contact us with any requests you may have.
Project.TT-03946