Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Abstract

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is an attractive research field in tumor immunotherapy. While CAR is genetically engineered to express certain molecules, it retains the intrinsic ability to recognize tumor cells through its own receptors. Additionally, NK cells do not depend on T cell receptors for cytotoxic killing. CAR-NK cells exhibit some differences to CAR-T cells in terms of more precise killing, numerous cell sources, and increased effectiveness in solid tumors. However, some problems still exist with CAR-NK cell therapy, such as cytotoxicity, low transfection efficiency, and storage issues. Immune checkpoints inhibit immune cells from performing their normal killing function, and the clinical application of immune checkpoint inhibitors for cancer treatment has become a key therapeutic strategy. The application of CAR-T cells and immune checkpoint inhibitors is being evaluated in numerous ongoing basic research and clinical studies. Immune checkpoints may affect the function of CAR-NK cell therapy. In this review, we describe the combination of existing CAR-NK cell technology with immune checkpoint therapy and discuss the research of CAR-NK cell technology and future clinical treatments. We also summarize the progress of clinical trials of CAR-NK cells and immune checkpoint therapy.

Immune checkpoint inhibitors: breakthroughs in cancer treatment

“…N-803, an IL-15 superagonist, has been shown to expand NK cells in humans after injection and to be well tolerated 51 . An ongoing clinical trial (NCT04847466) 52 is investigating the combination of N-803, pembrolizumab, and HSC CAR-NK for the treatment of GEJ and advanced HNSCC; trial completion is expected by the end of 2025.…”

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies

“…CAR-NK cell immunotherapy is an interesting area of research in cancer immunotherapy. 157 Natural killer (NK) cells are lymphocyte-derived natural immune cells that aim at modified host cells or cancer- and virus-infected cells. NK cells destroy target cells directly instead of damaging normal healthy cells.…”

Steering the course of CAR T cell therapy with lipid nanoparticles

“…No doubt the research in clinics concerning CAR natural killer (NK) cell therapy is advancing with a primary focus on augmenting its antitumor efficacy. Research findings underscore the merits of CAR NK cells, including their ability for precise tumor targeting, diverse cell origins, and enhanced effectiveness in combating solid tumors [ 4 – 6 ]. Researchers are actively addressing hurdles such as cytotoxicity, low transfection rates, and challenges related to storage linked with CAR NK cell therapy [ 7 ].…”