Advanced Cell Therapy Centre

Patients and the clinical need are always the basis for the development of new treatments. ACTC participates actively in the research and development of new advanced cell therapy products (ATMPs) in cooperation with domestic and foreign partners and is constantly looking for new collaborators in this area. ACTC can act as a contract development and/or manufacturing organization (CDMO) for products intended for clinical trials.

ACTC has good manufacturing practice (GMP)-level manufacturing facilities and processes that comply with the ATMP requirements. The personnel have profound expertise in the translational research, cell biology, GMP manufacturing and quality control of cell therapy products, as well as experience in the relevant regulation and cooperation with the competent authorities. ACTC personnel also actively engage in cell therapy related working groups, scientific communities, and research projects.

Current cell therapy products manufactured at the ACTC:

• Allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSC, or LY-MSC in Finnish) are used for the treatment of refractory graft-versus-host disease at hematopoietic transplantation centers in Finland. BM-MSCs are produced from the bone marrow of healthy voluntary donors. The BM-MSC product has been manufactured locally under hospital exemption since 2012. The preceding fruitful scientific research and knowledge on MSCs has enabled the successful establishment of this manufacturing process (g., Laitinen et al. 2016; Salmenniemi et al. 2017; Keto et al. 2018).
• Autologous keratinocytes are produced from patients’ own skin biopsy to treat severe burn injuries and wounds. The manufacturing process has been developed together with the clinicians and researchers at Helsinki Burn Centre, Helsinki University Hospital (HUS) and University of Helsinki (Knuutila et al. 2022).
• TCRα/β-CD19-depleted and CD34⁺ hematopoietic stem cell (HSC) -enriched grafts are produced for enabling safe HSC transplantations from haploidentical donors for pediatric patients. Graft engineering utilizes CliniMACS® Prodigy technology (Miltenyi Biotec) and has been set up in collaboration with the pediatricians at the Childrens’ Hospital in HUS.
• ACTC is a local contract manufacturer of chimeric antigen receptor (CAR) -T cells produced for multi-center clinical trials in Finland. In CAR-T cell therapy, the patient’s own T cells are modified so that the T cells are more effective in recognizing and destroying cancer cells. The advantage of local point-of-care production of CAR-T cells is that the cells are freshly handled and modified and thus, patients can receive the cells in a shorter time than in the centralized manufacturing of these products. ACTC has gained in-depth expertise in the manufacturing and quality control methods of CAR-T cells in the previous development projects.

Some relevant publications

Luostarinen A, Kailaanmäki A, Turkki V, Köylijärvi M, Käyhty P, Leinonen H, Albers-Skirdenko V, Lipponen E, Ylä-Herttuala S, Kaartinen T, Lesch H.P., Kekarainen T. Optimizing lentiviral vector formulation conditions for efficient ex vivo transduction of primary human T cells in chimeric antigen receptor T-cell manufacturing. Cytotherapy (in press). https://doi.org/10.1016/j.jcyt.2024.04.002

Delgadillo J, Kerkelä E, Waters A, van den Akker E, Lechanteur C, Baudoux E, Gardiner N, De Vos J, Vives J. A management model in blood, tissue and cell establishments to ensure rapid and sustainable patient access to advanced therapy medicinal products in Europe. Cytotherapy 2023, 25(12):1259-1264. https://doi.org/10.1016/j.jcyt.2023.08.001

Nuutila K, Katayama S, Laitinen A, Siltanen A, Patrikoski M, Valtonen J, Kankainen M, Kerkelä E, Kaartinen T, Juteau S, Korhonen M, Vuola J, Kankuri E. ATMP-classified, scalable, autologous cell spray for the treatment of skin wounds and assessment of its effects on wound healing clinically and on molecular level. Burns, 2022, 49(5):1144-1156. doi: https://doi.org/10.1016/j.burns.2022.09.006

Koski J, Jahan F, Luostarinen A, Schenkwein D, Ylä-Herttuala S, Göös H, Monzo H, Ojala PM, Maliniemi P and Korhonen M. Novel modular chimeric antigen receptor spacer for T cells derived from signal regulatory protein alpha Ig-like domains. Front. Mol. Med. 2022, 2:1049580. https://doi.org/10.3389/fmmed.2022.1049580

Keto J, Kaartinen T, Salmenniemi U, Castrén J, Partanen J, Hänninen A, Korhonen M, Lähteenmäki K, Itälä-Remes M, Nystedt J. Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety. Mol Ther Methods Clin Dev. 2018 Feb 8;9:109-118. https://doi.org/10.1016/j.omtm.2018.02.001

Salmenniemi U, Itälä-Remes M, Nystedt J, Putkonen M, Niittyvuopio R, Vettenranta K, Korhonen M. Good responses but high TRM in adult patients after MSC therapy for GvHD. Bone Marrow Transplant. 2017 Apr;52(4):606-608. https://doi.org/10.1038/bmt.2016.317

Laitinen A, Oja S, Kilpinen L, Kaartinen T, Möller J, Laitinen S, Korhonen M, Nystedt J. A robust and reproducible animal serum-free culture method for clinical-grade bone marrow-derived mesenchymal stromal cells. Cytotechnology. 2016 Aug;68(4):891-906. https://doi.org/10.1007/s10616-014-9841-x