The Cell Therapy Podcast KITE Gilead

In this episode we interview Dr. Johanna Olweus and Dr. Morten Milek Nielsen from University of Oslo about the use of T cell receptors (TCR’s) as immunotherapy against cancer.
 
Dr. Olweus’s group has been speadheading identifying TCRs that are specific for minute mutations in cancer cells, that can be used in adoptive T-cell-based therapies. We talk about what the therapy entails, how TCRs are discovered and go through several papers her group has published recently on using TCR-based therapies against leukemia.
 
The articles discussed are:
-       “Induction of neoantigen-reactive T cells from healthy donors” (link: https://pubmed.ncbi.nlm.nih.gov/31101906/)
-       “T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes” (Link: https://www.nature.com/articles/s41587-021-01089-x)
-       “A T cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo” (Link: https://www.nature.com/articles/s43018-023-00642-8)
-       “A systematic safety pipeline for selection of T-cell receptors to enter clinical use” (Link: https://pubmed.ncbi.nlm.nih.gov/37607971/)

You can read more about Dr. Olweus research group here: https://www.ous-research.no/olweus/

In this episode we talk to Dr. Rasmus O Bak from Aarhus University about the use of CRISPR and its use in cellular therapies. CRISPR has now become a method to not only knock gene’s out but - as Dr. Bak explains - also an all-round tool that can be utilized to a variety of different task. 

We discuss research from Dr. Bak’s research group, examining how CRISPRa and CRISPRi - a method to either active or inactivate genes - can be used in both hematopoietic stem cells and T cells to up- and down-regulate genes and push cells into entire new cellular states.

The articles discussed are:
“Targeted regulation of transcription in primary cells using CRISPRa and CRISPRi” (Link: https://genome.cshlp.org/content/31/11/2120.long)40-year-old associate professor is this year's recipient of the faculty's talent award (Link: https://biomed.au.dk/display/artikel/40-year-old-associate-professor-is-this-years-recipient-of-the-facultys-talent-award)“UK first to approve CRISPR treatment for diseases: what you need to know” (Link: https://www.nature.com/articles/d41586-023-03590-6)

What are NK cells, how do they function and how can we utilize them as a cellular therapy? In this episode we are joined by Dr Arnika K. Wagner and Dr Evren Alici, both from Center for Hematology and Regenerative Medicine at Karolinska Institutet, and Dr Sigrid Skånland from Institute for Cancer Research at Olso University Hospital for a chat about these exciting cells and how their anti-cancer effects are explored and can be used in the future.

In this episode we discuss the following articles:
Arnika K. Wagner et al, PD-1 expression on mouse intratumoral NK cells and its effects on NK cell phenotype, iScience, 2022Sigrid S Skånland et al,  Functional testing of relapsed chronic lymphocytic leukemia guides precision medicine and maps response and resistance mechanisms. An index case,  Haematologica, 2022.Hareth Nahi et al, Autologous NK cells as consolidation therapy following stem cell transplantation in multiple myeloma, Cell Reports Medicine, 2022.Arnika K. Wagner et al, Characterization of human natural killer cells for therapeutic use, Cytotherapy, 2019.Katharina H. Susek, Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy, Cancer Immunology, Immunotherapy, 2023.
You can follow Dr Sigrid S Skånland at @SigridSkanland and Dr Evren Alici at @ealici on Twitter.

What is precision medicine? How can cancer patients benefit from it, and what role does it play in cellular therapy? In this episode our guests Dr Caroline Heckman (Research Director for Institute for Molecular Medicine at University of Helsinki) and Dr Kjetil Tasken (Director, OUH Centre for Precision Medicine in Cancer at Oslo University Hospital) explore the role of precision medicine in hematological cancers and explain how they have set up clinical trials to test the efficacy of precision medicine in both Norway and Finland.
In this episode we discuss the following articles:
Åslaug Helland et al, Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway, Journal of Translational Medicine, 2022.Disha Malani et al,  Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia, Cancer Discovery, 2022.Mariaserena Giliberto et al, Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically, Molecular Oncology, 2022.
You can follow Dr Kertil Tasken @KjetilTasken and Dr Caroline Heckman at @HeckmanLab on Twitter. 

Chimeric antigen receptor therapy has revolutionized hematology but is there ways we could further improve the immune cells that delivery the therapy?

In this episode we talk to Professor Satu Mustjoki and Dr Olli Dufva and their recent paper ‘Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity’ (Link: https://ashpublications.org/blood/article/135/9/597/429647/Integrated-drug-profiling-and-CRISPR-screening) in Blood. We discuss how T cell responses are modified by drugs that could be used in combination with cellular therapies and how they can both enhance and inhibit CAR T cells functioning. We also get into the molecular mechanisms by which is thought to happen in a number of hematological cancer cells.

You can follow Dr. Olli Dufva and Profesor Mustjoki on twitter at: https://twitter.com/ollidufva and https://twitter.com/hruh_research. Read more about Professor Satu Mustjoki and her group here: https://www2.helsinki.fi/en/researchgroups/hematology-research-unit-helsinki/people

Solid tumour cells often use receptors such as PDL1 to block killing from immune cells. In this episode of the Cell Therapy Podcast we talk with Sébastien Wälchli, senior scientist at the Section for Cellular Therapy, Radiumhospitalet in Oslo, Norway about ways to bypass this cancer cell defense and how to improve CAR T cell therapy using combinatorial CARs.

We discuss two recent papers from Dr Wälchli’s group called ‘Built-in” PD-1 blocker to rescue NK-92 activity from PD-L1–mediated tumor escape mechanisms’ (link: https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202100025R) in FASEB and ‘Combinatorial CAR design improves target restriction’ (link: https://www.jbc.org/article/S0021-9258(20)00106-4/fulltext) in JBC.

Read more about professor Sébastien Wälchli and his research here: https://www.ous-research.no/home/cellulartherapy/Group+members+TR+Unit/8303.