Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside
Beibei Zhang,
Mengzhe Yang,
Weiming Zhang
et al.
Abstract:Immunotherapy has rapidly evolved in the past decades in the battle against cancer. Chimeric antigen receptor (CAR)-engineered T cells have demonstrated significant success in certain hematologic malignancies, although they still face certain limitations, including high costs and toxic effects. Natural killer cells (NK cells), as a vital component of the immune system, serve as the “first responders” in the context of cancer development. In this literature review, we provide an updated understanding of NK cell… Show more
“…These protocols often involve the use of cytokines such as IL-15 or a combination of IL-15, IL-21 and stem cell factor (SCF) to promote cell growth while maintaining cytotoxic capabilities [ 46 ]. Advances in gene editing technologies have also enabled more efficient insertion of CAR constructs into UCB-derived NK cells, enhancing their specificity and killing capacity against target cancer cells [ 47 – 51 ]. Despite the challenges, the ongoing optimization of techniques for the cultivation and genetic modification of UCB-derived NK cells continues to solidify their role as a valuable resource in the development of innovative immunotherapies.…”
Cancer immunotherapy harnesses the body’s immune system to combat malignancies, building upon an understanding of tumor immunosurveillance and immune evasion mechanisms. This therapeutic approach reactivates anti-tumor immune responses and can be categorized into active, passive, and combined immunization strategies. Active immunotherapy engages the immune system to recognize and attack tumor cells by leveraging host immunity with cytokine supplementation or vaccination. Conversely, passive immunotherapy employs exogenous agents, such as monoclonal antibodies (anti-CTLA4, anti-PD1, anti-PD-L1) or adoptive cell transfers (ACT) with genetically engineered chimeric antigen receptor (CAR) T or NK cells, to exert anti-tumor effects. Over the past decades, CAR-T cell therapies have gained significant traction in oncological treatment, offering hope through their targeted approach. However, the potential adverse effects associated with CAR-T cells, including cytokine release syndrome (CRS), off-tumor toxicity, and neurotoxicity, warrant careful consideration. Recently, CAR-NK cell therapy has emerged as a promising alternative in the landscape of tumor immunotherapy, distinguished by its innate advantages over CAR-T cell modalities. In this review, we will synthesize the latest research and clinical advancements in CAR-NK cell therapies. We will elucidate the therapeutic benefits of employing CAR-NK cells in oncology and critically examine the developmental bottlenecks impeding their broader application. Our discussion aims to provide a comprehensive overview of the current status and future potential of CAR-NK cells in cancer immunotherapy.
“…These protocols often involve the use of cytokines such as IL-15 or a combination of IL-15, IL-21 and stem cell factor (SCF) to promote cell growth while maintaining cytotoxic capabilities [ 46 ]. Advances in gene editing technologies have also enabled more efficient insertion of CAR constructs into UCB-derived NK cells, enhancing their specificity and killing capacity against target cancer cells [ 47 – 51 ]. Despite the challenges, the ongoing optimization of techniques for the cultivation and genetic modification of UCB-derived NK cells continues to solidify their role as a valuable resource in the development of innovative immunotherapies.…”
Cancer immunotherapy harnesses the body’s immune system to combat malignancies, building upon an understanding of tumor immunosurveillance and immune evasion mechanisms. This therapeutic approach reactivates anti-tumor immune responses and can be categorized into active, passive, and combined immunization strategies. Active immunotherapy engages the immune system to recognize and attack tumor cells by leveraging host immunity with cytokine supplementation or vaccination. Conversely, passive immunotherapy employs exogenous agents, such as monoclonal antibodies (anti-CTLA4, anti-PD1, anti-PD-L1) or adoptive cell transfers (ACT) with genetically engineered chimeric antigen receptor (CAR) T or NK cells, to exert anti-tumor effects. Over the past decades, CAR-T cell therapies have gained significant traction in oncological treatment, offering hope through their targeted approach. However, the potential adverse effects associated with CAR-T cells, including cytokine release syndrome (CRS), off-tumor toxicity, and neurotoxicity, warrant careful consideration. Recently, CAR-NK cell therapy has emerged as a promising alternative in the landscape of tumor immunotherapy, distinguished by its innate advantages over CAR-T cell modalities. In this review, we will synthesize the latest research and clinical advancements in CAR-NK cell therapies. We will elucidate the therapeutic benefits of employing CAR-NK cells in oncology and critically examine the developmental bottlenecks impeding their broader application. Our discussion aims to provide a comprehensive overview of the current status and future potential of CAR-NK cells in cancer immunotherapy.
“…NK cells, a specialized subset of innate lymphoid cells (ILCs), can distinguish between self-cells and non-self-cells through the recognition of self-major histocompatibility complex (MHC) I molecules [ 12 , 13 ]. They constitute approximately 10–15% of the lymphocyte population in peripheral blood, and characterized as large granular lymphocytes with kidney-shaped nuclei, a high cytoplasm-to-nucleus ratio, and large azurophilic granules in cytoplasm [ 14 , 15 ].…”
Section: Nk Cells: Biology Receptors and Functionsmentioning
confidence: 99%
“…They constitute approximately 10–15% of the lymphocyte population in peripheral blood, and characterized as large granular lymphocytes with kidney-shaped nuclei, a high cytoplasm-to-nucleus ratio, and large azurophilic granules in cytoplasm [ 14 , 15 ]. NK cell development and maturation primarily occur in the bone marrow, where common lymphoid progenitors (CLPs) differentiate into NK precursors (NKPs), immature NK cells, and finally mature NK cells [ 12 ]. Notably, recombinant interleukin (rIL)-15 plays a crucial role in NK cell development from hematopoietic stem cells [ 16 ].…”
Section: Nk Cells: Biology Receptors and Functionsmentioning
Non-Hodgkin lymphomas (NHLs) are heterogeneous and are among the most common hematological malignancies worldwide. Despite the advances in the treatment of patients with NHLs, relapse or resistance to treatment is anticipated in several patients. Therefore, novel therapeutic approaches are needed. Recently, natural killer (NK) cell-based immunotherapy alone or in combination with monoclonal antibodies, chimeric antigen receptors, or bispecific killer engagers have been applied in many investigations for NHL treatment. The functional defects of NK cells and the ability of cancerous cells to escape NK cell-mediated cytotoxicity within the tumor microenvironment of NHLs, as well as the beneficial results from previous studies in the context of NK cell-based immunotherapy in NHLs, direct our attention to this therapeutic strategy. This review aims to summarize clinical studies focusing on the applications of NK cells in the immunotherapy of patients with NHL.
In recent years, advancements in microbial sequencing technology have sparked an increasing interest in the bacteria residing within solid tumors and its distribution and functions in various tumors. Intratumoral bacteria critically modulate tumor oncogenesis and development through DNA damage induction, chronic inflammation, epigenetic alterations, and metabolic and immune regulation, while also influencing cancer treatment efficacy by affecting drug metabolism. In response to these discoveries, a variety of anti‐cancer therapies targeting these microorganisms have emerged. These approaches encompass oncolytic therapy utilizing tumor‐associated bacteria, the design of biomaterials based on intratumoral bacteria, the use of intratumoral bacterial components for drug delivery systems, and comprehensive strategies aimed at the eradication of tumor‐promoting bacteria. Herein, this review article summarizes the distribution patterns of bacteria in different solid tumors, examines their impact on tumors, and evaluates current therapeutic strategies centered on tumor‐associated bacteria. Furthermore, the challenges and prospects for developing drugs that target these bacterial communities are also explored, promising new directions for cancer treatment.
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