Recording and summary of the Cancer IO Sebinar session “Ex vivo models in IO research” is now available!
In the first edition of the Cancer IO Sebinar series we heard about the latest development of patient-derived ex vivo models in an immuno-oncology setting, and discussed about the possible future use of these models in clinical decision making.
Our invited speakers and panelists were David Barbie from Dana-Farber Cancer Institute & Harvard Medical School, Johana Kuncova-Kallio from UMP Biomedicals, Peeter Karihtala from Helsinki University Hospital and Jeroen Pouwels from University of Helsinki.
Watch the recording or read the webinar notes below written by M.D. Sini Luoma.
Introduction to Ex vivo models (3:20 in the video)
Jeroen Pouwels, Research Coordinator in Cancer IO, gave the introduction to ex vivo models. Preclinical drug study models are important especially in cancer research, because over 90 % of the cancer drugs fail in clinical development. There are many different approaches for ex vivo drug testing. Because of more accurate dimensions, 3D cell lines are better than 2D models but still they fail to capture the heterogeneity of the tumor environment. Cancer organoids represent a 3D structure of the tumor tissue.
There are a lot of immunotherapies in clinical research. Their huge advantage is the ability to cure the patient in some cases. To be able to test the immune therapies, one needs to have the immune system cells in the test model. Mouse models have been used but they are not ideal, and some mice are immunodeficient. Many drugs that are very efficient in mice are not effective at all in humans.
Patient-derived explant cultures (PDECs) are derived from authentic tumor and include tumor cells and immune cells. PDECs therefore can retain a functional immune contexture. However, one problem with PDEC is that there can be a lot of heterogeneity between the original tumor and the metastases, making it difficult to predict if the drug tested in PDEC derived from one tumor site will be effective in other tumors of the patient.
3D solutions and tissue preservation (16:36)
Johanna Kuncova-Kallio, Director in UPM Biomedicals, gave a talk about 3D solutions and tissue preservation. As an example, she presented a nanocellulose component (GrowDex) that can be used as a cell carrier. When preparing organoids, an automated 3D printing of the models can be used.
Ex vivo systems incorporating the tumor microenvironment (28:55)
Dr. David Barbie gave a thorough presentation about ex vivo systems incorporating the tumor microenvironment. The tumor microenvironment is important, because in addition to cancer cells also the other cells, like stromal and immune cells, actively contribute to tumor survival, growth and drug resistance. The dynamics of the tumor microenvironment are not captured by one moment, and most of the published research lacks the time dimension. The problem is that repeated tumor biopsies are invasive, and not predictive. To try to predict if the patient will respond to immune therapy, for example patient-derived xenografts and organoids can be used.
The tumor-specific expansion can be achieved within weeks to months, which is often too long a time for decision-making in patients with relapsed cancer. Dr. Barbie stated that the novel ex-vivo technologies will enable predictive functional precision medicine. Results will be available in a few days, which is fast enough for relapsing cancer.
For the interesting panel discussion hosted by Cancer IO’s Communications Manager Heidi Haikala, see the video from 1:28:24.
Relevant publications by Dr Barbie:
Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids. Cancer Discov. 2018 Feb;8(2):196-215. doi: 10.1158/2159-8290.CD-17-0833. Epub 2017 Nov 3.PMID: 29101162
Engineering approaches for studying immune-tumor cell interactions and immunotherapy. iScience. 2020 Dec 23;24(1):101985.doi: 10.1016/j.isci.2020.101985.