CAR T cell development

T cells modified with chimeric antigen receptors (CAR) have shown remarkable efficacy in the treatment of B-lineage acute lymphoblastic leukemia and lymphomas in both adults and children.

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.

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

Jahan FA, Koski J, Schenkwein D, Ylä-Herttuala S, Göös H, Huuskonen S, Varjosalo M, Maliniemi P, Leitner J, Steinberger P, Bühring H-J, Vettenranta K, Korhonen M. Using the Jurkat Reporter T cell line for Evaluating the Functionality of Novel Chimeric Antigen Receptors. Front. Mol. Med 3, 2023; doi: 10.3389/fmmed.2023.1070384
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.
Koski J, Jahan F, Luostarinen A, Schenkwein D, Ylä-Herttuala S, Göös H, Monzo H, Ojala PM, Maliniemi P, Korhonen, M. Novel Modular Chimeric Antigen Receptor Spacer for T cells Derived from Signal Regulatory Protein alpha Ig-like Domains. Front Mol Med 2, 2022; doi: 10.3389/fmmed.2022.1049580
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.
Salter AI, Pont MJ, Riddell SR. Chimeric antigen receptor – modified T cells : CD19 and the road beyond. Blood. 2018;131(24):2621–30.

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

Dr. Farhana is an accomplished researcher, having earned her Ph.D. in Biochemistry and Immunology from the University of Helsinki in 2019. Her thesis, titled “Phosphorylation of the α-chain in the integrin LFA-1 enables β2-chain phosphorylation and α-actinin binding required for cell adhesion,” underscores her significant contributions to the field of biochemistry and immunology.

Farhana is deeply committed to advancing scientific understanding and medical treatments. Her expertise is particularly pronounced in CAR T-cell therapy, where she focuses on refining Chimeric Antigen Receptor (CAR) technology. Her research is dedicated to developing targeted solutions for both hematological and solid tumor malignancies, with a meticulous exploration of CAR T-cell intracellular signaling to enhance precision and efficacy.

In addition to her work with CAR T-cells, Dr. Farhana is currently engaged in pioneering efforts involving Natural Killer (NK) cells. She is leveraging advanced bi and tri-cistonic CAR technology to enhance the efficacy of NK cells, with a specific focus on addressing neuroblastoma and other solid tumors.