Current Progress of CAR-NK Therapy in Cancer Treatment DOI Open Access

Zhaojun Pang,

Zhongyi Wang, Fengqi Li

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(17), P. 4318 - 4318

Published: Sept. 2, 2022

CD8+ T cells and natural killer (NK) eliminate target through the release of lytic granules Fas ligand (FasL)-induced cell apoptosis. The introduction chimeric antigen receptor (CAR) makes these two types selective effective in killing cancer cells. success CAR-T therapy treatment acute lymphoblastic leukemia (ALL) other blood cancers proved that immunotherapy is an approach fighting against cancers, yet adverse effects, such as graft versus host disease (GvHD) cytokine syndrome (CRS), cannot be ignored for therapy. CAR-NK therapy, then, has its advantage lacking effects works terms killing. Despite these, NK are known to hard transduce, expand vitro, sustain shorter vivo comparing infiltrated Moreover, faces challenges does, e.g., time, cost, potential biohazard due use animal-derived products. Thus, enormous efforts needed develop safe, effective, large-scalable protocols obtaining Here, we reviewed current progress including biological properties, CAR compositions, preparation cells, clinical progresses. We also discussed safety issues raised from genetic engineering. hope this review instructive research community a broad range readers.

Language: Английский

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances DOI Creative Commons
Karama Makni‐Maalej, Maysaloun Merhi,

Varghese Inchakalody

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Jan. 30, 2023

In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This consists of genetically engineered immune cells expressing surface receptor, called CAR, that specifically targets antigens expressed on tumor cells. hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T shown efficacy in treating chemotherapy refractory patients. However, value this remains inconclusive context solid tumors is restrained by several obstacles including limited trafficking infiltration, presence an immunosuppressive microenvironment, well adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) CAR-macrophages (CAR-M) were introduced complement/alternative for tumors. CAR-NK could be favorable substitute since they do not require HLA compatibility have toxicity. Additionally, might generated large scale from sources which would suggest them off-the-shelf product. CAR-M immunotherapy its capabilities phagocytosis, tumor-antigen presentation, broad currently being investigated. Here, we discuss emerging role CAR-T, CAR-NK, We also highlight advantages drawbacks compared Finally, prospective solutions potential combination therapies enhance CAR-cells immunotherapy.

Language: Английский

Citations

301
Natural killer cell homing and trafficking in tissues and tumors: from biology to application DOI Creative Commons
Guanghe Ran,

Yu qing Lin,

Lei Tian

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 29, 2022

Abstract Natural killer (NK) cells, a subgroup of innate lymphoid act as the first line defense against cancer. Although some evidence shows that NK cells can develop in secondary tissues, mainly bone marrow (BM) and egress into blood circulation when they mature. They then migrate to settle down peripheral though special subsets home back BM or organs. Owing its success allogeneic adoptive transfer for cancer treatment “off-the-shelf” potential, cell-based immunotherapy is attracting increasing attention various cancers. However, insufficient infiltration adoptively transferred limits clinical utility, especially solid tumors. Expansion engineered chimeric antigen receptor (CAR) ex vivo prior by using cytokines alters profiles chemokine receptors, which affects tumor tissue. Several factors control cell trafficking homing, including cell-intrinsic (e.g., transcriptional factors), cell-extrinsic integrins, selectins, chemokines their corresponding signals induced cytokines, sphingosine-1-phosphate (S1P), etc.), cellular microenvironment. Here, we summarize mechanisms homing at steady state during development, aiming improve immunotherapy.

Language: Английский

Citations

156
CAR-NK cells for cancer immunotherapy: from bench to bedside DOI Creative Commons
Leisheng Zhang, Meng Yuan, Xiaoming Feng

et al.

Biomarker Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: March 18, 2022

Abstract Natural killer (NK) cells are unique innate immune and manifest rapid potent cytotoxicity for cancer immunotherapy pathogen removal without the requirement of prior sensitization or recognition peptide antigens. Distinguish from T lymphocyte-based cythotherapy with toxic side effects, chimeric antigen receptor-transduced NK (CAR-NK) adequate to simultaneously improve efficacy control adverse effects including acute cytokine release syndrome (CRS), neurotoxicity graft-versus-host disease (GVHD). Moreover, considering inherent properties cells, CAR-NK “off-the-shelf” product satisfying clinical demand large-scale manufacture attribute cytotoxic effect via both cell receptor-dependent CAR-dependent signaling cascades. In this review, we mainly focus on latest updates cell-based tactics, together opportunities challenges immunotherapies, which represent paradigm boosting system enhance antitumor responses ultimately eliminate malignancies. Collectively, summarize highlight auspicious improvement in will benefit preclinical investigations adoptive immunotherapy.

Language: Английский

Citations

134
Glioblastoma Treatment: State-of-the-Art and Future Perspectives DOI Open Access
Alejandro Rodríguez-Camacho, José Guillermo Flores-Vázquez, Júlia Moscardini-Martelli

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7207 - 7207

Published: June 29, 2022

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, management based on maximal safe surgical resection, radiotherapy, chemotherapy with temozolomide. Recently, bevacizumab been added to treatment arsenal for recurrent scenario. Nevertheless, patients still have a poor prognosis. Therefore, efforts are being made different clinical areas find new alternative improve overall survival, free-progression life quality patients. (2) Methods: Our objective recap actual state-of-the-art treatment, resume future perspectives immunotherapy, as well synthetic molecules natural compounds that represent potential therapies at preclinical stages. (3) Conclusions: Despite great therapeutic research, suffered minimal changes, prognosis remains poor. Combined strategies delivery methods, including molecules, compounds, stem cell inhibition, may potentiate standard care therapy next step research.

Language: Английский

Citations

84
Forks in the road for CAR T and CAR NK cell cancer therapies DOI
Oula K. Dagher, Avery D. Posey

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 1994 - 2007

Published: Nov. 27, 2023

Language: Английский

Citations

67
Breakthrough of solid tumor treatment: CAR-NK immunotherapy DOI Creative Commons
Wenkang Wang, Yang Liu, Zhen He

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 20, 2024

Language: Английский

Citations

49
Cancer-associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosis via iron regulation DOI Creative Commons

Lizhong Yao,

Junyi Hou,

Xiongyan Wu

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102923 - 102923

Published: Oct. 6, 2023

As the predominant immunosuppressive component within tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) inhibit Natural Killer cell (NK cell) activity to promote progression and immune escape; however, mechanisms of cross-talk between CAFs NK cells in gastric cancer (GC) remain poorly understood. In this study, we demonstrate that levels are inversely correlated with abundance human GC. impair anti-tumor capacity by inducing ferroptosis, a death process characterized accumulation iron-dependent lipid peroxides. induce ferroptosis promoting iron overload; conversely, decreased intracellular protect against CAF-induced ferroptosis. Mechanistically, increase labile pool via export into TME, which is mediated upregulated expression regulatory genes ferroportin1 hephaestin CAFs. Moreover, CAF-derived follistatin like protein 1(FSTL1) upregulates NCOA4 DIP2A-P38 pathway, NCOA4-mediated ferritinophagy required for patient-derived organoid model, functional targeting using combination deferoxamine FSTL1-neutralizing antibody significantly alleviate boost cytotoxicity This study demonstrates novel mechanism suppression TME presents potential therapeutic approach augment response GC cells.

Language: Английский

Citations

48
Evolution of cell therapy for renal cell carcinoma DOI Creative Commons
Yufei Wang, Eloah Rabello Suarez, Gabriella Kastrunes

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 9, 2024

Treatment 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 therapies. However, curative treatment, particularly advanced-stage disease, remains rare. Cell as a "living drug" achieved hematological malignancy cures high response rate, significant research efforts have been made facilitate its translation solid tumors. Herein, we overview cellular therapies RCC focusing on allogeneic hematopoietic stem transplantation, T receptor gene-modified cells, chimeric antigen (CAR) CAR natural killer (NK) lymphokine-activated (LAK) γδ dendritic vaccination. We also included perspectives using other recent approaches, such macrophages, cell-cytokine induced cells regulatory CAR-T shed light preclinical development advancing into clinic achieve RCC.

Language: Английский

Citations

35
CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity DOI Creative Commons
Yaxian Kong, Jingyao Li,

Xia Zhao

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Chimeric Antigen Receptor (CAR)-T cell therapy has rapidly emerged as a groundbreaking approach in cancer treatment, particularly for hematologic malignancies. However, the application of CAR-T solid tumors remains challenging. This review summarized development technologies, emphasized challenges and solutions tumors. Also, key innovations were discussed including specialized CAR-T, combination therapies novel use CAR-Treg, CAR-NK CAR-M cells. Besides, CAR-based have extended its reach beyond oncology to autoimmune disorders. We reviewed preclinical experiments clinical trials involving Car-Treg CAAR-T various diseases. By highlighting these cutting-edge developments, this underscores transformative potential CAR technologies practice.

Language: Английский

Citations

3
The next wave of cellular immunotherapies in pancreatic cancer DOI Creative Commons
Dannel Yeo, Caroline Giardina, Payal Saxena

et al.

Molecular Therapy — Oncolytics, Journal Year: 2022, Volume and Issue: 24, P. 561 - 576

Published: Feb. 1, 2022

Pancreatic cancer is an aggressive disease that predicted to become the second leading cause of cancer-related death worldwide by 2030. The overall 5-year survival rate around 10%. typically presents late with locally advanced or metastatic disease, and there are limited effective treatments available. Cellular immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has had significant success in treating hematological malignancies. However, CAR therapy efficacy pancreatic been limited. This review provides overview current ongoing clinical studies major challenges strategies improve efficacy. These include arming cells; developing off-the-shelf allogeneic using other immune cells, like natural killer cells tumor-infiltrating lymphocytes; combination therapy. Careful incorporation preclinical models will enhance management affected individuals, assisting cellular immunotherapies. A multifaceted, personalized approach involving immunotherapy treatment required outcomes.

Language: Английский

Citations

62