Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Dec. 18, 2024
Language: Английский
Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)
Published: Jan. 2, 2025
Abstract Background Due to the lack of effective treatment options, prognosis patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains poor. Although chimeric antigen receptor (CAR)-T-cell therapy has shown promising effects in lymphoblastic (ALL) and lymphoma, its application R/R AML is limited by “off-target” effects, which lead severe bone marrow suppression limit clinical application. CAR-natural killer (NK) cells not only exhibit antitumor but also demonstrate increased safety universality. We have developed a new CAR construct that targets CD33 modified NK cells, specifically eliminating while reducing side on stem cells. Methods The CD33-targeting domain was selected CAR-T this optimized subsequently transduced into umbilical cord-derived via retroviral vector. Preclinical efficacy studies were conducted both vitro vivo. Ten eligible aged 18–65 years who received one or more infusions anti-CD33 CAR-NK following preconditioning regimen enrolled. assessed response rates treatment-related post-infusion, documenting long-term therapy. Results sequence basis CAR-T-cell demonstrated comparable showed toxicity hematopoietic (HSCs). patients, median five prior lines treatment, completed evaluation (range, 3–8). No grade 3–4 adverse events observed, except suppression, relieved within month. cases immune effector cell–associated neurotoxicity syndrome (ICANS) graft-versus-host disease (GVHD) reported cell infusion. Only patient experienced 2 cytokine release (CRS) presented persistent fever. By day 28, six ten had achieved minimal residual (MRD)-negative complete remission. Conclusions Our preclinical data primary for AML. Expanded samples longer follow-up periods are needed provide further data. Trial registration NCT05008575 ( https://clinicaltrials.gov/study/NCT05008575 ).
Language: Английский
Citations
2
Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)
Published: Aug. 5, 2024
Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.
Language: Английский
Citations
12
International Journal of Colorectal Disease, Journal Year: 2024, Volume and Issue: 40(1)
Published: Dec. 28, 2024
Abstract Purpose Colorectal cancer (CRC) remains one of the leading causes cancer-related mortality worldwide. Metastatic colorectal (mCRC) continues to present significant challenges, particularly in patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors. This narrative review aims provide recent developments immunotherapy for CRC treatment, focusing on its efficacy and challenges. Methods discussed various immunotherapeutic strategies including immune checkpoint inhibitors (ICIs) targeting PD-1 PD-L1, combination therapies involving ICIs other modalities, chimeric antigen receptor T-cell (CAR-T) cell therapy, vaccines. The role tumor microenvironment evasion mechanisms was also explored understand their impact effectiveness these therapies. Results provides a comprehensive update advancements CRC, highlighting potential approaches, inhibitors, therapies, CAR-T vaccination strategies. results MSI-H/dMMR tumors, which have improvements survival rates been observed. Furthermore, this addresses challenges faced treating pMMR/MSS resistant immunotherapy. Conclusion Immunotherapy plays treatment However, many remain, especially CRC. need further research into biomarker development, deeper understanding treatment.
Language: Английский
Citations
4
Scandinavian Journal of Immunology, Journal Year: 2025, Volume and Issue: 101(2)
Published: Feb. 1, 2025
Abstract Hepatocellular carcinoma (HCC) remains one of the most challenging malignancies globally, characterized by significant heterogeneity, late‐stage diagnosis, and resistance to treatment. In recent years, advent immune‐checkpoint blockades (ICBs) targeted immune cell therapies has marked a substantial advancement in HCC However, clinical efficacy these existing is still limited, highlighting urgent need for new breakthroughs. Natural killer (NK) cells, subset innate lymphoid family, have shown unique advantages anti‐tumour response. With increasing evidence suggesting crucial role dysfunctional NK cells pathogenesis progression HCC, considerable efforts been directed toward exploring as potential therapeutic target HCC. this review, we will provide an overview normal liver immunity followed detailed discussion various cell‐based immunotherapies their applications
Language: Английский
Citations
0
Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 639 - 639
Published: April 29, 2025
Cancer remains one of the leading causes mortality worldwide, with a growing need for precise and effective treatments. Traditional therapies such as chemotherapy radiotherapy have limitations, including off-target effects drug resistance. In recent years, targeted emerged promising alternatives, aiming to improve treatment specificity reduce systemic toxicity. Among most innovative approaches, bispecific antibodies, nanobodies, extracellular vesicles offer distinct complementary mechanisms cancer therapy. Bispecific antibodies enhance immune responses enable dual-targeting cells, nanobodies provide superior tumor penetration due their small size, present novel platform RNA delivery. This work aims review analyze these three assessing current applications, advantages, challenges, future perspectives.
Language: Английский
Citations
0
Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 846 - 846
Published: Oct. 21, 2024
Glioma is known for its immunosuppressive microenvironment, which makes it challenging to target through immunotherapies. Immune cells like macrophages, microglia, myeloid-derived suppressor cells, and T lymphocytes are infiltrate the glioma tumor microenvironment regulate immune response distinctively. Among variety of have highly complex multifaceted roles in landscape. lymphocytes, include CD4+ helper CD8+ cytotoxic their pivotal anti-tumor responses. However, these may behave differently dynamic example, via an invasion mechanism enforced by cells. Therefore, play dual immunity, firstly responses, secondly exploiting gliomas promote invasion. As immunosuppression strategy, induces T-cell exhaustion suppression effector regulatory (Tregs) or altering signaling pathways. Further, expression checkpoint inhibitors on cell surface leads anergy dysfunction. Overall, this interplay between crucial designing more effective The current review provides detailed knowledge helps explore novel therapeutic approaches reinvigorate lymphocytes.
Language: Английский
Citations
3
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: June 18, 2024
Citation: Sharma A, Rosato A and Schmidt-Wolf IGH (2024) Editorial: Cancer immunotherapies for hematologic malignancies - NK/CIK/CAR-T perspective. Front. Immunol. 15:1434259. doi: 10.3389/fimmu.2024.1434259
Language: Английский
Citations
0
Ageing & Longevity, Journal Year: 2024, Volume and Issue: 4 2024, P. 157 - 173
Published: Nov. 11, 2024
Chimeric Antigen Receptor (CAR) Natural Killer (NK) cells represent a promising advancement in cancer immunotherapy, particularly for targeting circulating tumor (CTCs) and preventing metastasis. This review examines the latest developments CAR NK cell therapy, including diverse sources, genetic engineering techniques, dual mechanisms of action. Targeting CTCs with shows significant potential aggressive cancers like triple-negative breast (TNBC) pancreatic cancer. The impact aging on function, especially regarding cytotoxicity, cytokine secretion, persistence, poses challenges elderly patients, but strategies such as interleukin-15 metabolic interventions offer solutions. also addresses current limitations, poor persistence immunosuppressive microenvironments low solid infiltration, while proposing combination therapies to enhance effectiveness. Although still earlier clinical stages compared T cells, cells’ safety profile MHC-independent recognition make them versatile therapeutic option. Future directions include optimizing improving developing age-adapted patients. _________________________________________________________________________________________ Keywords: Circulating (CTCs), Cell Therapy, Aging
Language: Английский
Citations
0
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Dec. 18, 2024
Language: Английский
Citations
0