In vitro OP9-DL1 co-culture and subsequent maturation in the presence of IL-21 generates tumor antigen-specific T cells with a favorable less-differentiated phenotype and enhanced functionality

• DOI: 10.1080/2162402x.2021.1954800
• Publication Date: 2021-07-25T07:10:32Z
• Authors: Sarah Bonte; Stijn de Munter; Lore Billiet; Glenn Goetgeluk; Joline Ingels; Hanne Jansen; Melissa Pille; Laurenz de Cock; Karin Weening; Tom Taghon; Georges Leclercq; Bart Vandekerckhove; Tessa Kerre
• Keywords: 0301 basic medicine; T-Lymphocytes; acute myeloid leukemia (aml); common gamma chain; 03 medical and health sciences; acute myeloid leukemia (AML); Antigens, Neoplasm; op9-dl1; Medicine and Health Sciences; t cell immunotherapy; Humans; common gamma chain cytokines; RC254-282; Original Research; RECEPTOR; T cell immunotherapy; Interleukins; PERSISTENCE; MATURE; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; CD8; MEMORY STEM-CELLS; RC581-607; cytokines; Coculture Techniques; hematopoietic stem cells; 3. Good health; NOTCH; OP9-DL1; Leukemia, Myeloid, Acute; Phenotype; HEMATOPOIETIC STEM; IL-15; CANCER REGRESSION; Immunologic diseases. Allergy; LEUKEMIA

T cell receptor (TCR)-redirected cells target intracellular antigens such as Wilms' tumor 1 (WT1), a tumor-associated antigen overexpressed in several malignancies, including acute myeloid leukemia (AML). For both chimeric (CAR)- and TCR-redirected cells, clinical studies indicate that subsets with less-differentiated phenotype (e.g. stem memory TSCM) survive longer mediate superior anti-tumor effects vivo opposed to more terminally differentiated cells. Cytokines added during vitro ex culture of play an important role driving the for adoptive transfer. Using OP9-DL1 co-culture system, we have shown previously are able generate vitro, starting from clinically relevant sources, single (TA)-specific TCR. This method circumvents possible TCR chain mispairing unwanted toxicities might occur when introducing TA-specific peripheral blood lymphocytes. We now show optimize our protocol, by adding IL-21 maturation, resulting generation enhanced effects. believe favorable TSCM-like these generated preludes persistence efficacy. Therefore, could be use valuable new form patient-tailored immunotherapy malignancies which finding suitable CAR-T is challenging, AML.