Chimeric antigen receptor (CAR)-engineered NK92 cells were surface cross-linked with liposomal vesicles carrying paclitaxel and demonstrated superior tumor control in mice, facilitated by CAR-NK cell accumulation at the tumor site, IFN-γ release by CAR-NK cells in response to cognate antigen, specific killing of tumor cells, and targeted delivery of low-dose paclitaxel, indicating a synergistic combination of immunotherapy and chemotherapy.
The therapeutic limitations of conventional chemotherapeutic drugs include chemo-resistance, tumor recurrence, and metastasis. Numerous nanoparticle-based active targeting approaches have emerged to enhance the intracellular concentration of drugs in tumor cells; however, efficient delivery of these systems to the tumor site while sparing healthy tissue remains elusive. Recently, much attention has been given to human immune-cell-directed nanoparticle drug delivery, because immune cells can traffic to the tumor and inflammatory sites. Natural killer cells are a subset of cytotoxic lymphocytes that play critical roles in cancer immunosurveillance. Engineering of the human natural killer cell line, NK92, to express chimeric antigen receptors to redirect their antitumor specificity has shown significant promise. We demonstrate that the efficacy of chemotherapy can be enhanced in vitro and in vivo while reducing off-target toxicity by using chimeric antigen receptor-engineered NK92 cells as carriers to direct drug-loaded nanoparticles to the target site.
Author Info: (1) Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA. (2) Department of Pharmacology and Pharmaceutical Sciences, University of S
Author Info: (1) Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA. (2) Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA. (3) Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA. (4) Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA. (5) Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA. (6) Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA. (7) Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA. (8) Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: pinwang@usc.edu.
