CAR-NK cells for cancer immunotherapy: recent advances and future directions

Abstract

Natural Killer (NK) cells, intrinsic to the innate immune system, are pivotal in combating cancer due to their independent cytotoxic capabilities in antitumor immune response. Unlike predominant treatments that target T cell immunity, the limited success of T cell immunotherapy emphasizes the urgency for innovative approaches, with a spotlight on harnessing the potential of NK cells. Despite tumors adapting mechanisms to evade NK cell-induced cytotoxicity, there is optimism surrounding Chimeric Antigen Receptor (CAR) NK cells. This comprehensive review delves into the foundational features and recent breakthroughs in comprehending the dynamics of NK cells within the tumor microenvironment. It critically evaluates the potential applications and challenges associated with emerging CAR-NK cell therapeutic strategies, positioning them as promising tools in the evolving landscape of precision medicine. As research progresses, the unique attributes of CAR-NK cells offer a new avenue for therapeutic interventions, paving the way for a more effective and precise approach to cancer treatment.

Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

“…CAR-NK cells offer potential solutions to the challenges faced by CAR-T cell therapy because they identify target cells without MHC restrictions, do not cause graft-versus-host disease (GVHD), can be obtained from different sources, such as allogeneic pluripotent stem cells or umbilical cord blood, and do not induce CRS or ICANS. Like CAR-T cells, CAR-NK cells undergo genetic modification to express CARs designed to recognize specific antigens present on target cells, including costimulatory domains [ 180 ].…”

CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges

“…A crucial aspect of CAR-NK cell therapy is its potential to be used as an "off-the-shelf" product, offering versatile and readily available treatment options. This characteristic is particularly beneficial in the clinical setting as it circumvents the need for patient-specific matching or lymphodepletion procedures [11]. It significantly simplifies the treatment process, potentially making it accessible to a broader patient population and reducing time and costs associated with therapy customization.…”

“…Once activated, NK cells unleash cytotoxic granules, containing molecules like perforin and granzymes, which facilitate the direct killing of target cells, mirroring the cytotoxic approach of CAR-T cells [41]. This dual-action mechanism endows CAR-NK cells with a unique advantage, enabling them to effectively eradicate cancer cells, even those lacking the specific antigen recognized by the CAR [11]. This capability renders CAR-NK cells exceptionally effective and versatile in combating diverse tumor cell populations, enhancing their potential as a formidable tool in cancer immunotherapy [28].…”

“…Conversely, CAR-NK therapy, which is emerging as a promising alternative, shows potential in both hematological malignancies and solid tumors [45]. CAR-NK cells can mediate their effects through both CAR-dependent and independent mechanisms, potentially offering broader tumor recognition and less susceptibility to the immunosuppressive effects of the tumor microenvironment [11]. Moreover, CAR-NK cells have been associated with fewer severe side effects, such as cytokine release syndrome and neurotoxicity, compared to CAR-T cells, highlighting their potential for a safer profile in cancer immunotherapy [12].…”

“…These receptors are designed to broaden the specificity and versatility of CAR-NK cells, enabling them to target multiple tumor antigens simultaneously and respond more effectively to various signals within the tumor microenvironment [87]. This strategy could be pivotal in enhancing the targeting accuracy of CAR-NK cells, potentially overcoming one of the major hurdles in cancer immunotherapy -the adaptability of tumors [11].…”