A Panorama of Immune Fighters Armored with CARs in Acute Myeloid Leukemia DOI Open Access
Ilias Christodoulou, Elena E. Solomou

Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 3054 - 3054

Published: June 5, 2023

Acute myeloid leukemia (AML) is a devastating disease. Intensive chemotherapy the mainstay of treatment but results in debilitating toxicities. Moreover, many treated patients will eventually require hematopoietic stem cell transplantation (HSCT) for disease control, which only potentially curative challenging option. Ultimately, subset relapse or have refractory disease, posing huge challenge to further therapeutic decisions. Targeted immunotherapies hold promise relapsed/refractory (r/r) malignancies by directing immune system against cancer. Chimeric antigen receptors (CARs) are important components targeted immunotherapy. Indeed, CAR-T cells achieved unprecedented success r/r CD19+ malignancies. However, modest outcomes clinical studies on AML. Natural killer (NK) innate anti-AML functionality and can be engineered with CARs improve their antitumor response. CAR-NKs associated lower toxicities than cells; however, efficacy AML has not been extensively investigated. In this review, we cite from describe limitations safety concerns. depict preclinical landscape CAR used alternative platforms specific focus CAR-NKs, providing insight into future optimization

Language: Английский

Targeting TIGIT for cancer immunotherapy: recent advances and future directions DOI Creative Commons
Peng Zhang, Xinyuan Liu,

Zhuoyu Gu

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 16, 2024

Abstract As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4 + cells, CD8 natural killer (NK) regulatory cells (Tregs), tumor-infiltrating lymphocytes (TILs). TIGIT has been associated NK exhaustion in vivo individuals various cancers. It not only modulates survival but also mediates exhaustion. the primary ligand of humans, CD155 may be main target for immunotherapy due to its interaction TIGIT. found that anti-programmed death protein 1 (PD-1) treatment response cancer correlated Anti-TIGIT alone combination anti-PD-1 agents have tested immunotherapy. Although two clinical studies advanced lung had positive results, TIGIT-targeted antibody, tiragolumab, recently failed new trials. In this review, we highlight current developments discuss characteristics functions

Language: Английский

Citations

32
Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy DOI Creative Commons

Fatemeh Dehghan,

Yekta Metanat,

Mandana Askarizadeh

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 11, 2025

Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy solid tumors, lethal adverse effects, high cost of autologous products, and the risk GvHD in allogeneic settings. As a potential alternative, CAR-NK can overcome most limitations provide off-the-shelf, safer, more affordable product. Although published results from preclinical clinical studies cells are promising, bottlenecks must be unlocked to maximize effectiveness therapy. These include vivo persistence, trafficking into tumor sites, modest sensitivity immunosuppressive microenvironment. In recent years, advances gene manipulation tools strategies have laid groundwork current This review will introduce existing discuss their advantages disadvantages. We also explore how these enhance therapy’s safety efficacy.

Language: Английский

Citations

3
Chimeric antigen receptor engineered natural killer cells for cancer therapy DOI Creative Commons
Yalan Zhang, Weilin Zhou, Jianping Yang

et al.

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 10, 2023

Abstract Natural killer (NK) cells, a unique component of the innate immune system, are inherent killers stressed and transformed cells. Based on their potent capacity to kill cancer cells good tolerance healthy NK have been successfully employed in adoptive cell therapy treat patients. In recent years, clinical success chimeric antigen receptor (CAR)-T has proven vast potential gene-manipulated as main force fight cancer. Following lessons learned from mature gene-transfer technologies advanced strategies CAR-T therapy, rapidly explored promising candidate for CAR-based therapy. An exponentially growing number studies multiple sources CAR-NK target wide range cancer-related antigens, showing remarkable outcomes encouraging safety profiles. Clinical trials also shown impressive therapeutic efficacy treatment hematological tumors, but solid tumors is still initial stages. this review, we present favorable profile platform engineering then summarize therapies up-to-date preclinical investigations. Finally, evaluate challenges remaining describe existing that can assist us devising future prospective solutions.

Language: Английский

Citations

29
NK cell defects: implication in acute myeloid leukemia DOI Creative Commons
Selma Z. D’Silva, Meenakshi Singh, Andrea S. Pinto

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 9, 2023

Acute Myeloid Leukemia (AML) is a complex disease with rapid progression and poor/unsatisfactory outcomes. In the past few years, focus has been on developing newer therapies for AML; however, relapse remains significant problem. Natural Killer cells have strong anti-tumor potential against AML. This NK-mediated cytotoxicity often restricted by cellular defects caused disease-associated mechanisms, which can lead to progression. A stark feature of AML low/no expression cognate HLA ligands activating KIR receptors, due these tumor evade lysis. Recently, different cell implicated in treating AML, such as adoptive NK transfer, Chimeric antigen receptor-modified (CAR-NK) therapy, antibodies, cytokine, drug treatment. However, data available scarce, outcomes vary between transplant settings types leukemia. Moreover, remission achieved some only short time. this mini-review, we will discuss role progression, particularly surface markers, therapies, results from various preclinical clinical trials.

Language: Английский

Citations

17
Beyond CAR T cells: exploring alternative cell sources for CAR-like cellular therapies DOI Creative Commons
Christina Angeliki Tsiverioti, Adrian Gottschlich, Marcel P. Trefny

et al.

Biological Chemistry, Journal Year: 2024, Volume and Issue: 405(7-8), P. 485 - 515

Published: May 20, 2024

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 alternative sources for CAR-based therapies, natural killer cells (NK), macrophages (MΦ), invariant Natural Killer T (iNKT) cells, γδT neutrophils, induced pluripotent stem (iPSC), emerged a promising avenue. By harnessing these cells' inherent cytotoxic mechanisms incorporating CAR technology, common CAR-T cell-related limitations can be effectively mitigated. We herein present an overview tumoricidal mechanisms, designs, processes CAR-NK CAR-MΦ, CAR-iNKT CAR-γδT CAR-neutrophils, iPSC-derived CAR-cells, outlining advantages, limitations, potential solutions therapeutic strategies.

Language: Английский

Citations

8
CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer DOI Open Access
Marta Włodarczyk, Beata Pyrzyńska

Cancers, Journal Year: 2022, Volume and Issue: 15(1), P. 117 - 117

Published: Dec. 24, 2022

Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly treating hematological neoplasms. However, graft-versus-host disease (GVHD) other adverse effects, such as cytokine release syndromes (CRS) neurotoxicity associated with CAR-T infusion, have raised some concerns about the broad application of this therapy. Natural killer (NK) cells identified promising alternative platforms for CAR-based therapies because their unique features, a lack human leukocyte (HLA)-matching restriction, superior safety, better activity when compared cells. The CRS, neurotoxicity, or GVHD, case CAR-NK therapy, addition to possibility using allogeneic NK CAR platform “off-the-shelf” opens new windows strategic opportunities. This review underlines design achievements constructs summarizes preclinical studies’ results regarding therapies’ safety potency. Additionally, approaches technology are briefly described, currently registered clinical trials listed.

Language: Английский

Citations

25
Universal CAR 2.0 to overcome current limitations in CAR therapy DOI Creative Commons

Lara Sophie Schlegel,

Coralie Werbrouck,

Michael Boettcher

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 19, 2024

Chimeric antigen receptor (CAR) T cell therapy has effectively complemented the treatment of advanced relapsed and refractory hematological cancers. The remarkable achievements CD19- BCMA-CAR therapies have raised high expectations within fields hematology oncology. These groundbreaking successes are propelling a collective aspiration to extend reach CAR beyond B-lineage malignancies. Advanced technologies created momentum surmount limitations conventional concepts. Most importantly, innovations that enable combinatorial targeting address target heterogeneity, using versatile adapter concepts in conjunction with recent transformative next-generation design, offer promise overcome both bottleneck associated manufacturing patient-individualized regimens. In this comprehensive review, we delineate fundamental prerequisites, navigate through pivotal challenges, elucidate strategic approaches, all aimed at paving way for future establishment multitargeted immunotherapies universal technologies.

Language: Английский

Citations

5
Advances in CAR-NK cell therapy for hematological malignancies DOI Creative Commons
Rui Yang,

Yun Yang,

Rui Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 28, 2024

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application introduced new challenges, such as safety concerns, off-target toxicities, significant costs. Natural killer (NK) cells are crucial components innate immune system, capable eliminating tumor without prior exposure to specific antigens or pre-activation. This inherent advantage complements limitations cells, making CAR-NK a promising avenue for immunotherapy. In recent years, preclinical clinical studies have yielded preliminary evidence supporting efficacy in paving way future advancements review aims succinctly discuss characteristics, therapeutic progress, potential challenges associated with therapy.

Language: Английский

Citations

5
Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities DOI Open Access
Yongfeng Chen, Jing Li,

Linglong Xu

et al.

World Journal of Clinical Cases, Journal Year: 2023, Volume and Issue: 11(2), P. 268 - 291

Published: Jan. 11, 2023

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays role in reducing relapse and improving long-term survival. With rapid advancements basic research molecular biology immunology with deepening understanding of the biological characteristics cells, allo-HSCT has been widely applied clinical practice. During allo-HSCT, preconditioning, donor, source cells can be tailored to patient's conditions, greatly broadening indications HSCT, clear survival benefits. However, risks associated remain high, i.e. reconstitution failure, delayed immune reconstitution, graft-versus-host disease, post-transplant relapse, which are bottlenecks further improvements efficacy have become hot topics field HSCT. Other recognized current individuals diagnosed leukemia subjected include selection most appropriate conditioning regimen post-transplantation management. In this paper, we reviewed progress relevant regarding these aspects.

Language: Английский

Citations

12
CRISPR-Cas9 in basic and translational aspects of cancer therapy DOI
Maryam Samareh Salavatipour,

Zahra Poursalehi,

Negin Hosseini Rouzbahani

et al.

Bioimpacts, Journal Year: 2024, Volume and Issue: 14(6), P. 30087 - 30087

Published: March 10, 2024

The discovery of gene editing techniques has opened a new era within the field biology and enabled scientists to manipulate nucleic acid molecules. CRISPR-Cas9 genome engineering revolutionized this achievement by successful targeting DNA molecule its sequence. Since genomic changes are basis birth growth many tumors, method been successfully applied identify genes which involved in initiating driving some neoplastic processes.

Language: Английский

Citations

4