Unleashing the Power of Precision Part II: Personalized medicine as strategy to target unmet medical needs.
von Michael Schell
Why looking at the immune system and its dynamicity might help to understand the mode of action of a disease or a treatment?
Understanding the immune system is key to understand diseases and infections. Already in 1908, Paul Ehrlich received the Nobel Prize for Medicine in the field of immunology together with Ilja Metschnikow for the work on the side-chain theory which established as basic principle of immunity (3). Further in 2018, the Nobel Prize was granted the two immunologists Jim Allison and Tasuku Honjo in the emerging field of immunotherapy for their outstanding discovery of cancer therapy by inhibition of negative immune regulation. The aim of immunotherapy is to enable T-cells to attack the tumor and hence to undergo the body own protection for self-immunity (4). Recently, Katalin Karikó and Drew Weissman jointly received the Nobel Prize in Medicine in the year 2023 for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19 (5).
The highly innovative CAR-T-cell therapy approach is one example of immunotherapy. CAR-T stands for “chimeric antigen receptor T-cells”. Generally, tumor cells are not attacked by T-cells because of molecular protection and hence the immune system is blind for these targets. In the process of the CAR-T-cell therapy, patient-derived “blind” T-cells are genetically engineered outside the patient in a special environment (classically a highly regulated clean room that demands special needs in puncto precision, stay tune for upcoming articles on this) to see those targets and they are trained to attack and kill. The improved CAR-T-cells are then injected back into the patient to chase down the now visible tumor cells. Recognition is possible because the cells carry the chimeric antigen receptor binding to dedicated tumor antigens on the surface of tumor cells.
Although immunotherapy has substantially increased the survival, just a percentage of patients respond to the treatment. Furthermore, some cancer entities are associated with very poor response to immunotherapy, increasing the need to explore new strategies and to combine existing ones. By using high content imaging techniques cellular interactions and cellular dynamics reveal cell-biological mechanisms and the molecular players regulating cancer immunotherapy (6).
For example, while CAR T-cell therapy efficiently has been established for leukemia, these therapies are less efficient for solid tumors and new preclinical models are still needed. In 2019, Henner Farin and his team at the Georg Speyer House, Frankfurt, could develop a model for CAR-mediated cytotoxicity against 3-dimensional (3D) patient-derived colorectal cancer organoids and showed for the first time successful destruction of colon cancer cells by genetically modified immune cells (7).
Cenibra wants to assist you in your research quest to understand the immune system and our looking-at-cells technologies have proved to be big benefit for streamlining your work (8, 9).
Recently, Cenibra has been supporting the LION (Leipzig Immune Oncology) Conference, 2023 with a booth and a collaborative poster from Dr. Eliana Stanganello and her group at TRON, Mainz (see the poster below). The poster nicely describes parts of their work with the CQ and how they want to determine the immune system to understand the modes of action of a killing reaction. Amazingly, high detailed images of a tumor cell - NK cell interaction are presented, and you can see how the NK cell is destroying its target after polarizing towards it.
High content imaging and assessment of cellular dynamics using the CQ1 confocal microscope.
In the past, high content imaging and analysis required highly sophisticated and very voluminous equipment. Furthermore, image analysis used to be very time consuming and laborious.
The CQ1 Confocal Imaging Cytometer from Yokogawa provides access to benchmark quality high content data from 2D and 3D cellular assays for any lab benchtop. Screening experiments on multiwell plates are possible as well as its use as a very fancy microscope for slides or dishes, the CQ1 and the respective analysis software CellPathFinder bring amazing insights to any cell lab.
The latest generation of Yokogawa´s patented microlens-enhanced spinning disc CSU-W1 combines amazing speed with reduced cell damage, and the option for robotic integration offers remarkable throughput when needed.
Further, where precision and speed is needed our other looking-at-cell technologies such as the Celigo or the Cellaca are highly useful in this and in other research fields, too. In one of our next blog article we are going to emphazise how we can maximize your experiment efficiency by combining the technologies and by setting up screening assays for you lab.
References:
- : https://lac.cenibra.de/en/blogpost/high-content-analysis-understanding-sars-cov-2-infection-of-cells
- : https://lac.cenibra.de/en/cq1-virology
- : https://de.wikipedia.org/wiki/Paul_Ehrlich
- : https://www.nobelprize.org/prizes/medicine/2018/allison/facts/
- : https://www.nobelprize.org/prizes/medicine/2023/press-release/
- : High content imaging and assessment of cellular dynamics using the CQ1 confocal microscope, Poster, TRON
- : Schnalzger T.E. et al. 3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids. In: The EMBO Journal (online publication 29th April 2019). DOI: 15252/embj.2018100928
- : Heim C., et. al. ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma. Front. Immunol. 14:1228894. doi: 10.3389/fimmu.2023.1228894
- : Bodden, M.; et. al. Co-Expression of an IL-15 Superagonist Facilitates Self-Enrichment of GD2-Targeted CAR-NK Cells and Mediates Potent Cell Killing in the Absence of IL-2. Cancers 2023, 15, 4310. https://doi.org/10.3390/cancers15174310