{Reference Type}: Journal Article
{Title}: CD70-specific CAR NK cells expressing IL-15 for the treatment of CD19-negative B-cell malignancy.
{Author}: Guo S;Lei W;Jin X;Liu H;Wang JQ;Deng W;Qian W;
{Journal}: Blood Adv
{Volume}: 8
{Issue}: 11
{Year}: 2024 Jun 11
{Factor}: 7.637
{DOI}: 10.1182/bloodadvances.2023012202
{Abstract}: <B>UNASSIGNED: </B>Chimeric antigen receptor (CAR) natural killer (NK) cells can eliminate tumors not only through the ability of the CAR molecule to recognize antigen-expressed cancer cells but also through NK-cell receptors themselves. This overcomes some of the limitations of CAR T cells, paving the way for CAR NK cells for safer and more effective off-the-shelf cellular therapy. In this study, CD70-specific (a pan-target of lymphoma) fourth-generation CAR with 4-1BB costimulatory domain and interleukin-15 (IL-15) was constructed and transduced into cord blood-derived NK cells by Baboon envelope pseudotyped lentiviral vector. CD70-CAR NK cells displayed superior cytotoxic activity in vitro and in vivo against CD19-negative B-cell lymphoma when compared with nontransduced NK cells and CD19-specific CAR NK cells. Importantly, mice that received 2 doses of CD70-CAR NK cells showed effective eradication of tumors, accompanied by increased concentration of plasma IL-15 and enhanced CAR NK cell proliferation and persistence. Our study suggests that repetitive administration-based CAR NK-cell therapy has clinical advantage compared with a single dose of CAR NK cells for the treatment of B-cell lymphoma.