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Journal articles on the topic 'CAR-Natural Killer and CAR-macrophages'

Author: Grafiati

Published: 7 June 2025

Last updated: 2 August 2025

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1

Smolarska, Anna, Zuzanna Kokoszka, Marcelina Naliwajko, et al. "Cell-Based Therapies for Solid Tumors: Challenges and Advances." International Journal of Molecular Sciences 26, no. 12 (2025): 5524. https://doi.org/10.3390/ijms26125524.

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Solid tumors pose significant therapeutic challenges due to their resistance to conventional treatments and the complexity of the tumor microenvironment. Cell-based immunotherapies offer a promising approach, enabling precise, personalized treatment through immune system modulation. This review explores several emerging cellular therapies for solid tumors, including tumor-infiltrating lymphocytes, T cell receptor-engineered T cells, CAR T cells, CAR natural killer cells, and macrophages. Tumor-infiltrating lymphocytes and their modified versions, T cell receptor-engineered T cells and CAR T ce

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Gayatri Jaiswal, Rajani Dubey, and Krishna Kumar Prajapati. "Leukemia its origin, types, risk factors and survivorship." World Journal of Biology Pharmacy and Health Sciences 18, no. 1 (2024): 283–92. http://dx.doi.org/10.30574/wjbphs.2024.18.1.0083.

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Leukemia cancer; Feline leukemia virus (FeLV); CAR-Natural Killer and CAR-macrophages; TPMT and NUDT15 genes; Thiopurines.Leukemia is a cancer of the body’s blood forming tissues such as bone marrow and the lymphatic system. It is most common cancer in the children but mostly occur in adults.The general symptoms in leukemia cancer are appetite and headaches, and red patches on the skin of patients.The hematopoietic stem cell help to regenerate the healthy and leukemia free cells of white blood cells in bone marrow of patients and slowly-slowly cure the leukemia patients. Feline leukemia virus

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Gayatri, Jaiswal, Dubey Rajani, and Kumar Prajapati Krishna. "Leukemia its origin, types, risk factors and survivorship." World Journal of Biology Pharmacy and Health Sciences 18, no. 1 (2024): 283–92. https://doi.org/10.5281/zenodo.13729523.

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Leukemia cancer; Feline leukemia virus (FeLV); CAR-Natural Killer and CAR-macrophages; TPMT and NUDT15 genes; Thiopurines.Leukemia is a cancer of the body’s blood forming tissues such as bone marrow and the lymphatic system. It is most common cancer in the children but mostly occur in adults.The general symptoms in leukemia cancer are appetite and headaches, and red patches on the skin of patients.The hematopoietic stem cell help to regenerate the healthy and leukemia free cells of white blood cells in bone marrow of patients and slowly-slowly cure the leukemia patients. Feline leukemia

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Du, Zhicheng, Sumin Zhu, Xi Zhang, Zhiyuan Gong, and Shu Wang. "Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment." Cancers 15, no. 3 (2023): 567. http://dx.doi.org/10.3390/cancers15030567.

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MM, characterized by the progressive accumulation of clonal plasma cells in bone marrow, remains a severe medical problem globally. Currently, almost all MM patients who have received standard treatments will eventually relapse. Autologous anti-BCMA CAR-T cells are one of the FDA-approved immunotherapy cell-based products for treating adults with relapsed or refractory (r/r) multiple myeloma. However, this type of CAR-T cell product has several limitations, including high costs, long manufacturing times, and possible manufacturing failure, which significantly hinder its wider application for m

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Xian, Yunjia, та Lu Wen. "CARBeyond αβ T Cells: Unleashing NK Cells, Macrophages, and γδ T Lymphocytes Against Solid Tumors". Vaccines 13, № 6 (2025): 654. https://doi.org/10.3390/vaccines13060654.

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Chimeric antigen receptor (CAR)-engineered cell therapy represents a landmark advancement in cancer immunotherapy. While αβ CAR-T therapy has demonstrated remarkable success in hematological malignancies, its efficacy in solid tumors remains constrained mainly by factors such as antigen heterogeneity, immunosuppressive microenvironments, and on-target/off-tumor toxicity. To overcome these limitations, emerging CAR platforms that utilize alternative immune effectors, including natural killer (NK) cells, macrophages, and γδ T lymphocytes, are rapidly gaining traction. This review systematically

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Shin, Min Hwa, Eunha Oh, Yunjeong Kim, et al. "Recent Advances in CAR-Based Solid Tumor Immunotherapy." Cells 12, no. 12 (2023): 1606. http://dx.doi.org/10.3390/cells12121606.

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Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design—such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells—have shown promising results in

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Lee, Jung Min. "When CAR Meets Stem Cells." International Journal of Molecular Sciences 20, no. 8 (2019): 1825. http://dx.doi.org/10.3390/ijms20081825.

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The generation of immune cells from human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) has been of keen interest to regenerative medicine. Pluripotent stem cell-derived immune cells such as natural killer cells, macrophages, and lymphoid cells, especially T cells, can be used in immune cell therapy to treat incurable cancers. Moreover, since the advent of chimeric antigen receptor (CAR) technology, the success of CAR-T cells in the clinic has galvanized new efforts to harness the power of CAR technology to generate CAR-engineered immune cells from pluripoten

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Uscanga-Palomeque, Ashanti Concepción, Ana Karina Chávez-Escamilla, Cynthia Aracely Alvizo-Báez, et al. "CAR-T Cell Therapy: From the Shop to Cancer Therapy." International Journal of Molecular Sciences 24, no. 21 (2023): 15688. http://dx.doi.org/10.3390/ijms242115688.

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Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we

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Fedorova, P. O. "CAR natural killer cell therapy: Natural killer cell activation and expansion." Acta Biomedica Scientifica 9, no. 5 (2024): 53–65. http://dx.doi.org/10.29413/abs.2024-9.5.6.

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Currently, chimeric antigen receptor (CAR) T-cell therapy is an effective treatment method of hematological malignancies. However, T-lymphocyte-based immunotherapy has certain limitations for the scope of application of this approach. A promising alternative is CAR therapy based on natural killer (NK) cells, since it does not require detailed donor selection according to the human leukocyte antigen system; NK cells have a unique mechanism for recognizing and destroying tumor cells. In addition, NK cells do not cause severe toxic reactions when infused. The creation of a CAR NK product is a com

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Moreno, Carlos, Christopher Haynie, Abigail Johnson, and K. Scott Weber. "Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer." Biomedicines 10, no. 7 (2022): 1493. http://dx.doi.org/10.3390/biomedicines10071493.

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For nearly three decades, chimeric antigen receptors (CARs) have captivated the interest of researchers seeking to find novel immunotherapies to treat cancer. CARs were first designed to work with T cells, and the first CAR T cell therapy was approved to treat B cell lymphoma in 2017. Recent advancements in CAR technology have led to the development of modified CARs, including multi-specific CARs and logic gated CARs. Other immune cell types, including natural killer (NK) cells and macrophages, have also been engineered to express CARs to treat cancer. Additionally, CAR technology has been ada

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Czaplicka, Agata, Mieszko Lachota, Leszek Pączek, Radosław Zagożdżon, and Beata Kaleta. "Chimeric Antigen Receptor T Cell Therapy for Pancreatic Cancer: A Review of Current Evidence." Cells 13, no. 1 (2024): 101. http://dx.doi.org/10.3390/cells13010101.

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Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of malignant and non-malignant disorders. CARs are synthetic transmembrane receptors expressed on genetically modified immune effector cells, including T cells, natural killer (NK) cells, or macrophages, which are able to recognize specific surface antigens on target cells and eliminate them. CAR-modified immune cells mediate cytotoxic antitumor effects via numerous mechanisms, including the perforin and granzyme pathway, Fas and Fas Ligand (FasL) pathway, and cytokine secretion. High hopes are associated with the

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Basar, Rafet, May Daher, and Katayoun Rezvani. "Next-generation cell therapies: the emerging role of CAR-NK cells." Hematology 2020, no. 1 (2020): 570–78. http://dx.doi.org/10.1182/hematology.2020002547.

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Abstract T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed the paradigm of treatment for many patients with relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T cell therapy in both the autologous and allogeneic settings, including practical, logistical, and toxicity issues. Given these concerns, there is a rapidly growing interest in natural killer cells as alternative vehicles for CAR engineering, given their unique biological features and their established safety profile in the all

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Basar, Rafet, May Daher, and Katayoun Rezvani. "Next-generation cell therapies: the emerging role of CAR-NK cells." Blood Advances 4, no. 22 (2020): 5868–76. http://dx.doi.org/10.1182/bloodadvances.2020002547.

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Abstract T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed the paradigm of treatment for many patients with relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T cell therapy in both the autologous and allogeneic settings, including practical, logistical, and toxicity issues. Given these concerns, there is a rapidly growing interest in natural killer cells as alternative vehicles for CAR engineering, given their unique biological features and their established safety profile in the all

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Klingemann, Hans. "Are natural killer cells superior CAR drivers?" OncoImmunology 3, no. 4 (2014): e28147. http://dx.doi.org/10.4161/onci.28147.

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Zhao, Yu, and Xiaorong Zhou. "Engineering chimeric antigen receptor-natural killer cells for cancer immunotherapy." Immunotherapy 12, no. 9 (2020): 653–64. http://dx.doi.org/10.2217/imt-2019-0139.

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Adoptive cell transfer has attracted considerable attention as a treatment for cancer. The success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells for the treatment of haematologic tumors has demonstrated the potential of CAR. In this review, we describe the current CAR-engineered natural killer (CAR-NK) cell construction strategies, including the design principles and structural characteristics of the extracellular, transmembrane and intracellular regions of the CAR structure. In addition, we review different cellular carriers used to develop CAR-NK cells, highlighting existing

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Chen, Yi-Ju, Bams Abila, and Yasser Mostafa Kamel. "CAR-T: What Is Next?" Cancers 15, no. 3 (2023): 663. http://dx.doi.org/10.3390/cancers15030663.

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The year 2017 was marked by the Food and Drug Administration (FDA) approval of the first two chimeric antigen receptor-T (CAR-T) therapies. The approved indications were for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and for the treatment of patients up to 25 years of age with acute lymphoblastic leukemia (ALL) that is refractory or in a second or later relapse. Since then, extensive research activities have been ongoing globally on different hematologic and solid tumors to assess the safety and efficacy of CAR-T therapy for these diseases. Limitations to CAR

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Golubovskaya, Vita, John Sienkiewicz, Jinying Sun, et al. "CAR-NK Cells Generated with mRNA-LNPs Kill Tumor Target Cells In Vitro and In Vivo." International Journal of Molecular Sciences 24, no. 17 (2023): 13364. http://dx.doi.org/10.3390/ijms241713364.

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Natural killer (NK) cells are cytotoxic lymphocytes that are critical for the innate immune system. Engineering NK cells with chimeric antigen receptors (CARs) allows CAR-NK cells to target tumor antigens more effectively. In this report, we present novel CAR mRNA-LNP (lipid nanoparticle) technology to effectively transfect NK cells expanded from primary PBMCs and to generate functional CAR-NK cells. CD19-CAR mRNA and BCMA-CAR mRNA were embedded into LNPs that resulted in 78% and 95% CAR expression in NK cells, respectively. BCMA-CAR-NK cells after transfection with CAR mRNA-LNPs killed multip

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Simon, Bianca, Manuel Wiesinger, Johannes März, et al. "The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of Melanoma." International Journal of Molecular Sciences 19, no. 8 (2018): 2365. http://dx.doi.org/10.3390/ijms19082365.

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Natural killer T (NKT) cells represent a cell subpopulation that combines characteristics of natural killer (NK) cells and T cells. Through their endogenous T-cell receptors (TCRs), they reveal a pronounced intrinsic anti-tumor activity. Thus, a NKT cell transfected with a chimeric antigen receptor (CAR), which recognizes a tumor-specific surface antigen, could attack tumor cells antigen-specifically via the CAR and additionally through its endogenous TCR. NKT cells were isolated from peripheral blood mononuclear cells (PBMCs), expanded, and electroporated with mRNA encoding a chondroitin sulf

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Chen, Sophia. "Releasing the brake in CAR natural killer cells." Blood 137, no. 5 (2021): 579–81. http://dx.doi.org/10.1182/blood.2020008993.

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Kloess, Stephan, Anna Kretschmer, Lilly Stahl, Stephan Fricke, and Ulrike Koehl. "CAR-Expressing Natural Killer Cells for Cancer Retargeting." Transfusion Medicine and Hemotherapy 46, no. 1 (2019): 4–13. http://dx.doi.org/10.1159/000495771.

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21

Corral Sánchez, María Dolores, Lucía Fernández Casanova, and Antonio Pérez-Martínez. "Beyond CAR-T cells: Natural killer cells immunotherapy." Medicina Clínica (English Edition) 154, no. 4 (2020): 134–41. http://dx.doi.org/10.1016/j.medcle.2019.08.004.

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Amoozgar, Behzad, Ayrton Bangolo, Charlene Mansour, et al. "Engineering Innate Immunity: Recent Advances and Future Directions for CAR-NK and CAR–Macrophage Therapies in Solid Tumors." Cancers 17, no. 14 (2025): 2397. https://doi.org/10.3390/cancers17142397.

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Adoptive cell therapies have transformed the treatment landscape for hematologic malignancies. Yet, translation to solid tumors remains constrained by antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and poor persistence of conventional CAR-T cells. In response, innate immune cell platforms, particularly chimeric antigen receptor–engineered natural killer (CAR-NK) cells and chimeric antigen receptor–macrophages (CAR-MΦ), have emerged as promising alternatives. This review summarizes recent advances in the design and application of CAR-NK and CAR-MΦ therapies for solid

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Qin, Vicky Mengfei, Criselle D’Souza, Paul J. Neeson, and Joe Jiang Zhu. "Chimeric Antigen Receptor beyond CAR-T Cells." Cancers 13, no. 3 (2021): 404. http://dx.doi.org/10.3390/cancers13030404.

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Chimeric antigen receptors (CAR) are genetically engineered receptors that can recognise specific antigens and subsequently activate downstream signalling. Human T cells engineered to express a CAR, also known as CAR-T cells, can target a specific tumour antigen on the cell surface to mediate a cytotoxic response against the tumour. CAR-T cell therapy has achieved remarkable success in treating hematologic malignancies, but not in solid tumours. Currently, extensive research is being carried out to make CAR-T cells a therapy for solid tumours. To date, most of the research interest in the fiel

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Jaing, Tang-Her, Yi-Wen Hsiao, and Yi-Lun Wang. "Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors." Current Issues in Molecular Biology 47, no. 2 (2025): 90. https://doi.org/10.3390/cimb47020090.

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Chimeric antigen receptor-T (CAR-T) cell therapy has demonstrated impressive efficacy in the treatment of blood cancers; however, its effectiveness against solid tumors has been significantly limited. The differences arise from a range of difficulties linked to solid tumors, including an unfriendly tumor microenvironment, variability within the tumors, and barriers to CAR-T cell infiltration and longevity at the tumor location. Research shows that the reasons for the decreased effectiveness of CAR-T cells in treating solid tumors are not well understood, highlighting the ongoing need for strat

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Di, Quan-shu, Tao Xu, Ying Song, et al. "High C-Reactive Protein to Albumin Ratio Predicts Inferior Clinical Outcomes in Extranodal Natural Killer T-Cell Lymphoma." Dose-Response 18, no. 2 (2020): 155932582091782. http://dx.doi.org/10.1177/1559325820917824.

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Objective: The prognostic value of C-reactive protein to albumin ratio (CAR) has been identified in several cancers but not in extranodal natural killer T-cell lymphoma (ENKTL) as yet. We aimed to evaluate the prognostic value of CAR in ENKTL. Methods: A retrospective study with 246 patients with ENKTL was performed to determine the prognostic value of pretreatment CAR and examine the prognostic performance of CAR incorporating with International Prognostic Index (IPI) or natural killer/T-cell lymphoma prognostic index (NKPI) by nomogram. Results: The Cox regression analyses showed that high C

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Rotolo, Ramona, Valeria Leuci, Chiara Donini, et al. "CAR-Based Strategies beyond T Lymphocytes: Integrative Opportunities for Cancer Adoptive Immunotherapy." International Journal of Molecular Sciences 20, no. 11 (2019): 2839. http://dx.doi.org/10.3390/ijms20112839.

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Chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR Ts) produced impressive clinical results against selected hematological malignancies, but the extension of CAR T cell therapy to the challenging field of solid tumors has not, so far, replicated similar clinical outcomes. Many efforts are currently dedicated to improve the efficacy and safety of CAR-based adoptive immunotherapies, including application against solid tumors. A promising approach is CAR engineering of immune effectors different from αβT lymphocytes. Herein we reviewed biological features, therapeutic potential, and sa

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Leivas, Alejandra, Paula Rio, Rebeca Mateos, et al. "NKG2D-CAR Transduced Primary Natural Killer Cells Efficiently Target Multiple Myeloma Cells." Blood 132, Supplement 1 (2018): 590. http://dx.doi.org/10.1182/blood-2018-99-114522.

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Abstract Introduction Immunotherapy represents a new weapon in the fight against multiple myeloma. Current clinical outcomes using CAR-T cell therapy against multiple myeloma show promise in the eradication of the disease. However, these CARs observe relapse as a common phenomenon after treatment due to the reemergence of neoantigens or negative cells. CARs can also be targeted using non-antibody approaches, including the use of receptors, as NKG2D with a wider range of ligands, and ligands to provide target specificity. Different cell types have been used to improve CAR cell therapy. CAR-T ce

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Testa, Ugo, Germana Castelli, and Elvira Pelosi. "Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies." Cancers 17, no. 9 (2025): 1454. https://doi.org/10.3390/cancers17091454.

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The clinical use of T lymphocytes engineered with chimeric antigen receptors (CARs) has revolutionized the treatment of patients with refractory or relapsed hematological malignancies. CAR natural killer (CAR-NK) cells are NK cells engineered with CARs to specifically target cell antigens expressed on the membrane of tumor cells. CAR-NK cells could offer some advantages with respect to CAR-T cells, related to their specific and innate anti-tumor activity, availability as an “off the shelf” cellular therapy, reduced costs, and improved safety. Promising efficacy of CAR-Nk cell therapy was obser

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Schindler-Wnek, Katharina, and Dominik Schmiedel. "CAR-NK-Zellen: die nächste Innovation der Krebsimmuntherapie?" BIOspektrum 31, no. 3 (2025): 280–83. https://doi.org/10.1007/s12268-025-2470-4.

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Abstract CAR-NK cells offer a promising immunotherapy approach, addressing key CAR-T cell limitations like reduced toxicity risks while retaining targeted efficacy. They combine the innate cytotoxicity of natural killer (NK) cells with the targeted action of chimeric antigen receptors (CAR). Their potential lies in efficacy, tolerability and the possibility of off-the-shelf production, enabling rapid treatment access. However, CAR-NK cells are still in early development with ongoing clinical trials. The next years will determine their potential for clinical application.

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Aftabizadeh, Maryam, Brenda Aguilar, Massimo D'Apuzzo, Behnam Badie, and Christine E. Brown. "Abstract A030: A deeper understanding of tumor microenvironment modulation induced by IL13Ra2 CAR T cells in a patient with grade 3 ependymoma." Cancer Immunology Research 13, no. 2_Supplement (2025): A030. https://doi.org/10.1158/2326-6074.io2025-a030.

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Abstract Grade 3 ependymoma is classified as a fast-growing solid tumor that often occurs in the base of the brain with a median survival of less than two years. Despite aggressive standard treatments (surgery, radiation therapy and chemotherapy), grade 3 ependymoma remains uniformly fatal, especially if the tumor cannot be completely removed or if it spreads to other areas of the central nervous system (CNS). Achieving a responsive therapy with chimeric antigen receptor (CAR) T cell therapy has been a significant challenge due to evasive tumor microenvironment, specifically utilized by slid t

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Kang, Kyung-Sun. "Abstract 2177: Spatial transcriptomic and functional analysis of HLA/PD-1/CTLA4 multi-gene edited CD19 CAR-iNK cells targeting pericytes in the glioblastoma tumor microenvironment to inhibit tumor migration and growth." Cancer Research 85, no. 8_Supplement_1 (2025): 2177. https://doi.org/10.1158/1538-7445.am2025-2177.

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Abstract Targeting glioblastoma (GBM) stem cell-derived pericytes in the perivascular niche offers a promising strategy to overcome intratumoral heterogeneity and inhibit tumor migration. By targeting CD19-positive pericytes, CD19 chimeric antigen receptor (CAR)-expressing natural killer (NK) cells can mitigate off-tumor toxicity; however, their interactions within the GBM tumor microenvironment (TME) require further investigation. In this study, we developed a GBM TME xenograft model by transplanting GBM-blood vessel assembloids (GBVA) into immunodeficient mice to study the effects of CD19 CA

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Shioya, Koichiro, Tomio Matsumura, Akane Urakami, et al. "Abstract 6105: iPSC-derived HER2 CAR-iNKT cells enhance the activity of immune cells against cancer cells." Cancer Research 85, no. 8_Supplement_1 (2025): 6105. https://doi.org/10.1158/1538-7445.am2025-6105.

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Abstract Invariant natural killer T (iNKT) cells directly kill tumor cells through TCR and NKG2D, and also exert anti-tumor activity indirectly by promoting dendritic cell (DC) maturation, activating CD8+T cells and repolarizing macrophages. iNKT cells do not trigger graft versus host disease, making them an attractive cell type for an “off-the-shelf” cell therapy platform. We are developing iPSC-derived iNKT (ipsNKT) cell therapy to overcome manufacturing challenges due to the low abundance of iNKT cells in blood. It is not clear whether ipsNKT cells, especially when the cells are gene edited

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Petty, Amy J., Benjamin Heyman, and Yiping Yang. "Chimeric Antigen Receptor Cell Therapy: Overcoming Obstacles to Battle Cancer." Cancers 12, no. 4 (2020): 842. http://dx.doi.org/10.3390/cancers12040842.

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Chimeric antigen receptors (CAR) are fusion proteins engineered from antigen recognition, signaling, and costimulatory domains that can be used to reprogram T cells to specifically target tumor cells expressing specific antigens. Current CAR-T cell technology utilizes the patient’s own T cells to stably express CARs and has achieved exciting clinical success in the past few years. However, current CAR-T cell therapy still faces several challenges, including suboptimal persistence and potency, impaired trafficking to solid tumors, local immunosuppression within the tumor microenvironment and in

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Ślebioda, Tomasz J., Marcin Stanisławowski, Lucyna Kaszubowska, Jan M. Zaucha, and Michał A. Żmijewski. "Current and Future Perspectives for Chimeric Antigen Receptor T Cells Development in Poland." Biomedicines 10, no. 11 (2022): 2912. http://dx.doi.org/10.3390/biomedicines10112912.

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Chimeric antigen receptor T (CAR-T) cells are genetically modified autologous T cells that have revolutionized the treatment of relapsing and refractory haematological malignancies. In this review we present molecular pathways involved in the activation of CAR-T cells, describe in details the structures of receptors and the biological activity of CAR-T cells currently approved for clinical practice in the European Union, and explain the functional differences between them. Finally, we present the potential for the development of CAR-T cells in Poland, as well as indicate the possible direction

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Allain, Vincent, Allison Rothrock, William Nyberg, et al. "Targeted Integration of a Chimeric Antigen Receptor in Key Selected Loci in Primary Natural Killer Cells." Blood 142, Supplement 1 (2023): 4807. http://dx.doi.org/10.1182/blood-2023-183080.

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Despite promising preclinical studies and early clinical data (Liu et al., NEJM, 2020), chimeric antigen receptor natural killer cells (CAR NK) are not yet on par with CAR T cells for the treatment of malignant diseases. Much effort has gone into developing NK-optimized CAR architectures (Li et al., Cell Stem Cell, 2018) and to increasing the persistence of CAR NK cells. We hypothesized that CAR NK cells could also benefit from the targeted integration of a CAR transgene, as compared with semi-random integration obtained using gammaretroviral vectors. Precise targeting has proven highly advant

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Li, Wangshu, Xiuying Wang, Xu Zhang, Aziz ur Rehman Aziz, and Daqing Wang. "CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges." Biomolecules 14, no. 8 (2024): 1035. http://dx.doi.org/10.3390/biom14081035.

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The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains

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Robbins, Gabrielle M., Kenta Yamamoto, Joshua Krueger, Walker Lahr, Joseph Skeate, and Branden Moriarity. "Abstract 2836: Genome engineered natural killer cell immunotherapy against osteosarcoma." Cancer Research 82, no. 12_Supplement (2022): 2836. http://dx.doi.org/10.1158/1538-7445.am2022-2836.

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Abstract Over the last decade Chimeric Antigen Receptor based T cell therapy (CAR-T) has developed into an effective immunotherapy for some cancers. Unfortunately, CAR-T cell therapies have several shortcomings and clinical success has primarily been limited to hematological cancers. Challenges of CAR-T cell therapy include tumor immune evasion through loss of target antigen expression by tumor cells and inhibition of CAR-T cell function by tumor expressed inhibitory molecules. Natural killer (NK) cells present an alternative to T cells that could be more effective due to their ability to perf

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Zhou, Yang, Miao Li, Kuangyi Zhou, et al. "Engineering-Induced Pluripotent Stem Cells for Cancer Immunotherapy." Cancers 14, no. 9 (2022): 2266. http://dx.doi.org/10.3390/cancers14092266.

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Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells

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Sayegh, Mark, Shoubao Ma, and Jianhua Yu. "Application of natural killer immunotherapy in blood cancers and solid tumors." Current Opinion in Oncology 35, no. 5 (2023): 446–52. http://dx.doi.org/10.1097/cco.0000000000000968.

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Purpose of review Natural killer (NK) cells are innate lymphoid cells characterized by their ability to attack aberrant and cancerous cells. In contrast to the activation of T-cells, NK cell activation is controlled by the interaction of NK cell receptors and their target cells in a manner independent of antigen organization. Due to NK cells’ broad array of activation cues, they have gained great attention as a potential therapeutic agent in cancer immunotherapy. Recent findings Ex vivo activation, expansion, and genetic modifications, such as the addition of a chimeric antigen receptor (CAR),

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Volarevic, Vladislav, Carl Randall Harrell, Aleksandar Arsenijevic, Valentin Djonov, and Ana Volarevic. "Effects of Mesenchymal Stem Cells on Functions of Chimeric Antigen Receptor-Expressing T Lymphocytes and Natural Killer Cells." Cells 14, no. 13 (2025): 978. https://doi.org/10.3390/cells14130978.

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Chimeric antigen receptor (CAR)-engineered immune cells, particularly CAR T lymphocytes and CAR natural killer (NK) cells, have revolutionized cancer immunotherapy. However, their therapeutic efficacy and safety can be influenced by the tumor microenvironment, particularly the presence of mesenchymal stem cells (MSCs). MSCs are immunomodulatory cells which can alter the function of tumor-infiltrated immune cells in both supportive and suppressive ways. Results obtained in recently conducted experimental studies demonstrate that MSCs modulate proliferation, cytotoxicity, cytokine production and

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Ye, Ziyun A. "The Advances and Challenges of CAR-NK Cells for Tumor Immunotherapy." E3S Web of Conferences 131 (2019): 01001. http://dx.doi.org/10.1051/e3sconf/201913101001.

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Immunotherapies using chimeric antigen receptor (CAR)-T cells bring an encouraging vision to non-Hodgkin lymphoma patients who develop relapsed lymphoma or are unresponsive to standard chemotherapy, yet they also have limitations and drawbacks. Clinical trials have reported cases of neurotoxicity and cytokine release syndrome (CRS) accompanied by CAR-T cell therapies. To establish a more mature therapy, CAR incorporated into Natural Killer (NK) cells came into being. As a leukocyte involved in innate immunity, NK cell does not require MHC matching, making the production of allogeneic “off-the-

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Bao, Chaolemeng, Quanli Gao, Lin-Lin Li, et al. "The Application of Nanobody in CAR-T Therapy." Biomolecules 11, no. 2 (2021): 238. http://dx.doi.org/10.3390/biom11020238.

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Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobodies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR structure has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural k

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Pfefferle, Aline, and Nicholas D. Huntington. "You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy." Cancers 12, no. 3 (2020): 706. http://dx.doi.org/10.3390/cancers12030706.

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The clinical success stories of chimeric antigen receptor (CAR)-T cell therapy against B-cell malignancies have contributed to immunotherapy being at the forefront of cancer therapy today. Their success has fueled interest in improving CAR constructs, identifying additional antigens to target, and clinically evaluating them across a wide range of malignancies. However, along with the exciting potential of CAR-T therapy comes the real possibility of serious side effects. While the FDA has approved commercialized CAR-T cell therapy, challenges associated with manufacturing, costs, and related to

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Tsiverioti, Christina Angeliki, Adrian Gottschlich, Sebastian Theurich, et al. "Beyond CAR T cells: exploring alternative cell sources for CAR-like cellular therapies." Biological Chemistry, May 21, 2024. http://dx.doi.org/10.1515/hsz-2023-0317.

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Abstract Chimeric antigen receptor (CAR)-T cell therapy has led to remarkable clinical outcomes in the treatment of hematological malignancies. However, challenges remain, such as limited infiltration into solid tumors, inadequate persistence, systemic toxicities, and manufacturing insufficiencies. The use of alternative cell sources for CAR-based therapies, such as natural killer cells (NK), macrophages (MΦ), invariant Natural Killer T (iNKT) cells, γδT cells, neutrophils, and induced pluripotent stem cells (iPSC), has emerged as a promising avenue. By harnessing these cells’ inherent cytotox

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Pan, Kevin, Hizra Farrukh, Veera Chandra Sekhar Reddy Chittepu, Huihong Xu, Chong-xian Pan, and Zheng Zhu. "CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy." Journal of Experimental & Clinical Cancer Research 41, no. 1 (2022). http://dx.doi.org/10.1186/s13046-022-02327-z.

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AbstractAdoptive cell therapy with chimeric antigen receptor (CAR) immunotherapy has made tremendous progress with five CAR T therapies approved by the US Food and Drug Administration for hematological malignancies. However, CAR immunotherapy in solid tumors lags significantly behind. Some of the major hurdles for CAR immunotherapy in solid tumors include CAR T cell manufacturing, lack of tumor-specific antigens, inefficient CAR T cell trafficking and infiltration into tumor sites, immunosuppressive tumor microenvironment (TME), therapy-associated toxicity, and antigen escape. CAR Natural Kill

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Azeez, Sarkar Sardar, Raya Kh Yashooa, Shukur Wasman Smail, et al. "Advancing CAR-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives." Molecular Cancer 24, no. 1 (2025). https://doi.org/10.1186/s12943-025-02386-8.

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Abstract Chimeric antigen receptor-cell therapies have demonstrated remarkable success in haematological malignancies but face significant hurdles in solid tumours. The hostile tumour microenvironment, antigen heterogeneity, limited tumour infiltration, and CAR-cell exhaustion contribute to reduced efficacy. Additionally, toxicity, off-target effects, and manufacturing challenges limit widespread clinical adoption. Overcoming these barriers requires a multifaceted approach that enhances CAR-cell persistence, trafficking, and tumour-specific targeting. Recent advancements in alternative cellula

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"CAR-Transduced Natural Killer Cells." New England Journal of Medicine 382, no. 19 (2020): 1865–67. http://dx.doi.org/10.1056/nejmc2004226.

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Andrea, Alain E., Andrada Chiron, Guillaume Sarrabayrouse, Stéphanie Bessoles, and Salima Hacein-Bey-Abina. "A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?" Frontiers in Immunology 15 (October 4, 2024). http://dx.doi.org/10.3389/fimmu.2024.1459818.

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In recent years, following the groundbreaking achievements of chimeric antigen receptor (CAR) T cell therapy in hematological cancers, and advancements in cell engineering technologies, the exploration of other immune cells has garnered significant attention. CAR-Therapy extended beyond T cells to include CAR natural killer (NK) cells and CAR-macrophages, which are firmly established in the clinical trial landscape. Less conventional immune cells are also making their way into the scene, such as CAR mucosal-associated invariant T (MAIT) cells. This progress is advancing precision medicine and

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Wang, Yufei, Eloah Rabello Suarez, Gabriella Kastrunes, et al. "Evolution of cell therapy for renal cell carcinoma." Molecular Cancer 23, no. 1 (2024). http://dx.doi.org/10.1186/s12943-023-01911-x.

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AbstractTreatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a “living drug” has achieved hematological malignancy cures with a high response rate, and significant research efforts have been made to facilitate its translation to solid tumors. Herein, we overview the cellular therapies for RCC focusing on allog

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Liu, Yong, Yifei Duan, Zefan Du, et al. "Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy." Experimental Hematology & Oncology 14, no. 1 (2025). https://doi.org/10.1186/s40164-025-00683-y.

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Abstract Chimeric antigen receptor (CAR) engineered cellular immunotherapy offers the potential for precise targeting and elimination of tumor cells, providing a tailored approach to cancer treatment. CAR-T cells demonstrate significant anti-tumor activity among these therapies. Nonetheless, these therapies may trigger adverse effects, including inflammatory and neurotoxic reactions during treatment. Recent efforts have been directed toward enhancing efficacy by optimizing CAR design or modulating its activity. Compared to CAR-T cells, CAR-engineered natural killer cells (CAR-NK) present notab

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