IL-27 IN A FOURTH GENERATION CAR ENHANCES CAR-NK CELL EFFECTOR FUNCTION

• Published in: Cytotherapy (Oxford, England) England), 2024-06, Vol.26 (6), p.S8-S8
• Main Authors: Biggi, A.F., Silvestre, R.N., Tirapelle, M.C., de Azevedo, J.T., Covas, D., Malmegrim, K.C., Figueiredo, M.L., Picanço-Castro, V.
• Format: Article
• Language: English
• Subjects: Cancer; CAR-NK; Immunotherapy
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2024.03.015

Interleukin 27 (IL-27), part of the IL-12 cytokine family, enhances NK cell cytotoxicity by inducing activating receptors (e.g., NKp46, NKG2D), and stimulating IFN-gamma production. While chimeric antigen receptor (CAR) has shown promise for NK cells in early-phase clinical trials, improving CAR-NK cell therapeutic effectiveness is critical. Although transgenic expression of cytokines (e.g., IL-15) in CAR-NK cells partially enhances pro-survival or proliferative properties, further research is needed to identify the optimal cytokine. Therefore, investigating the role of co-expressing IL-27 with a fourth-generation CD19-targeted CAR on NK cells is crucial. Lentiviral particles carrying CAR19 and CAR19-IL27 vectors were used to transduce NK-92 cell line. CAR+ cells were FACS-sorted and the potency of CAR-NK cells was evaluated against CD19+ cell lines (NALM-6 and Raji) both in vitro and in in vivo murine models. Tumor burden was quantified through bioluminescence. RNA from target-activated CAR19 and CAR19-IL27 was prepared following Illumina's TruSeq-stranded-mRNA protocol and conducted by LC Sciences. Our findings suggest that CAR19-IL27 enhances NK-92 inherent proliferative ability by about 4-fold compared to CAR19. Furthermore, CAR19-IL27 cells exhibited higher in vitro cytotoxicity against NALM-6 and Raji compared to CAR19, p