The CAR confers both target cell recognition as well as activation of the effector cell, thus equipping the body’s own immune system to effectively fight cancer. We have recently identified the cell culture components permitting optimal generation of CAR T-cells with an early memory phenotype, conferring improved persistence and anti-tumor effect of the cells in vivo. A screen of small molecule drugs identified candidate drugs that can potentially be used to enhance or control CAR T-cell activity in vivo.
The typical structure of a CAR is shown in Figure 1. We have designed a set of novel CAR backbones, designated FiCARs, and shown that functional CAR T-cells can be produced using these novel CAR genes, (Jan Koski, manuscript in preparation). The intellectual property rights for this invention will give us freedom to operate in this heavily patented field.
In our current work with CAR T-cells we endeavor to advance the FiCAR concept further in order to develop therapies for both B-lineage hematological malignancies and for solid tumors.
References:
1. Salter AI, Pont MJ, Riddell SR. Chimeric antigen receptor – modified T cells : CD19 and the road beyond. Blood. 2018;131(24):2621–30.
2. Kaartinen T, Luostarinen A, Maliniemi P, Keto J, Arvas M, Belt H, et al. Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion. Cytotherapy. 2017;19(6):689–702.
3. Dufva O, Koski J, Maliniemi P, Ianevski A, Klievink J, Leitner J, et al. Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity. Blood. 2020;135(9):597–609.
Researchers
Docent Matti Korhonen, MD, PhD
Docent Matti Korhonen’s background is in pediatrics, with 10 years’ clinical experience in pediatric hemato-oncology and stem cell transplantation. His research converges on the development and clinical translation of cell therapies. The Advanced Cell Therapy Center (at the Finnish Red Cross Blood Service) was set up under his leadership in 2009-12. He also led the development and clinical translation of its first cell therapy product, mesenchymal stem cells (Salmenniemi et al, Br Med J 2017).
Currently Dr. Korhonen’s research team focuses on the genetic modification of immune cells for cancer therapy, where they have explored novel culture conditions for CAR T-cells, combining CAR T-cells with small molecule drugs, and developed proprietary chimeric antigen receptors.
Jan Koski, MSc
Jan is a full time PhD student at the Finnish Red Cross Blood Service focusing his research on CAR-T cells by designing, testing and evaluating new receptors to enhance (CAR) the T cell responses and functionality in hematological malignancies and solid tumors. He has a Bachelor’s degree in laboratory sciences and a master’s degree in cell and molecular biology and he is aiming to finalize his PhD studies in 2022.
Manar Elmadani, PhD
Manar received her MSc in pharmaceutical sciences from Suez Canal University, Egypt, in 2012 and PhD in pharmacology and toxicology from the University of Oulu, Finland, in 2020. Her PhD research projects focused on the molecular mechanisms underlying cardiotoxicity of kinase inhibitors. Manar’s current research as post-doctoral researcher focuses on the development of CAR T-cells targeting solid tumors. Her aim is to be able to use CAR T-cells to treat solid tumors in the future.
Farhana Jahan, PhD
Farhana has a PhD focused in Biochemistry and Immunology from the University of Helsinki. She is interested in tumor immunology and the development of immunotherapeutics for hematological and solid tumor malignancies.
Currently she is involved in the development of CARs (Chimeric Antigen Receptor) for T-cells targeting hematological and solid malignancies specifically and efficiently. She also aims at understanding the mechanisms of CAR T-cell intracellular signaling and how to improve CAR T-cell trafficking and targeting against solid tumors. Farhana is also working on the development of NK cells as a therapeutic product for the hematological malignancies and neuroblastoma.
Marita Kaislaranta, MSc
Marita has recently completed her master’s degree in biology from University of Eastern Finland. The topic of her master’s thesis was the MGME1 exonuclease and it’s role in linear mtDNA degradation. She has also bachelor’s degree in health care in biomedical laboratory science. Marita started to work at Blood Service in 2012 as a biomedical laboratory technician at blood group laboratory. Currently Marita is involved in CAR-T cell project as a research assistant.
