使用表达共刺激分子和 IL-21 的饲养细胞对原代 NK 细胞进行体外扩增与转导

Natural Killer (NK) cells are an important population of the immune system, and NK cell-based therapy has shown great potential in the treatment of cancers.

However, to apply NK cells clinically, producing a large number of cells with high cytotoxicity remains a challenge. Current strategies focus on employing different irradiated feeder cells to stimulate NK expansion, maturation, and cytotoxicity.

While co-stimulatory signals play critical roles in promoting NK cell proliferation and activating their functions, the exploitation of these signals for expanding NK cells has not been fully explored. To identify the optimal engineered feeder cells for expanding umbilical cord blood-derived NK cells, we generated different feeder cells expressing the co-stimulatory molecules CD80, 4-1BBL, or membrane-bound IL-21 (mbIL21).

We then evaluated the transduction efficacy of a chimeric antigen receptor (CAR) construct into expanded NK cells using various lentiviral vectors.

Our results showed that CD80, in combination with 4-1BBL and mbIL21, induced the highest expansion of NK cells from cord blood. The expanded NK cells displayed higher cytotoxicity toward target cells compared to T cells following CAR transduction using BaEV lentivirus.