CAR T-Cell-Based gene therapy for cancers: new perspectives, challenges, and clinical developments

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Chimeric antigen receptor (CAR)-T cell therapy is a progressive new pillar in immune for cancer. It has yielded remarkable clinical responses patients with B-cell leukemia or lymphoma. Unfortunately, many challenges remain to be addressed overcome its ineffectiveness the treatment of other hematological and solidtumor malignancies. The major hurdles CAR T-cell are associated severe life-threatening toxicities such as cytokine release syndrome limited anti-tumor efficacy. In this review, we briefly discuss cancer immunotherapy genetic engineering T cells and, detail, current innovations strategies improve efficacy treating solid tumors hematologic Furthermore, also T-cell-derived nanovesicle therapy. Finally, included well.

Language: Английский

---

Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 7, 2022

The development of combination immunotherapy based on the mediation regulatory mechanisms tumor immune microenvironment (TIME) is promising. However, a deep understanding immunology must involve systemic environment (STIE) which was merely illustrated previously. Here, we aim to review recent advances in single-cell transcriptomics and spatial for studies STIE, TIME, their interactions, may reveal heterogeneity responses as well dynamic changes essential treatment effect. We evidence from preclinical clinical related significance overall survival, through different immunomodulatory pathways, such metabolic neuro-immunological pathways. also evaluate interactions after local radiotherapy or combined immunotherapy. focus our lung cancer, hepatocellular carcinoma, nasopharyngeal aiming reshape STIE TIME enhance efficacy.

Language: Английский

---

Targeting macrophages in hematological malignancies: recent advances and future directions

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Aug. 17, 2022

Abstract Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated escape. The most well-described are “don’t eat me” signals, including CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 MHC-I/LILRB1 axis. Molecules have been developed to block these pathways enhance phagocytic activity against tumors. Several clinical studies investigated safety efficacy CD47 blockades, either alone or combination with existing therapy hematological malignancies, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), lymphoma. However, only a minority patients responses treatments alone. Combining blockades other treatment modalities studies, early results suggesting synergistic therapeutic effect. Targeting macrophages bispecific antibodies being explored blood therapy. Furthermore, reprogramming pro-tumor anti-tumor macrophages, CAR (CAR-M) demonstrate activities. In this review, we elucidated distinct types macrophage-targeted strategies from preclinical experiments trials, outlined potential approaches developed.

Language: Английский

---

Exosomal circRNA: emerging insights into cancer progression and clinical application potential

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 26, 2023

Abstract Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune fibroblasts, other components, thereby regulating critical aspects of cancer progression including escape, angiogenesis, metabolism, drug resistance, proliferation metastasis. Interestingly, microenvironment have new findings in influencing escape mediated by the release exosomal circRNA. Given intrinsic stability, abundance, broad distribution circRNAs, they represent excellent diagnostic prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up possibilities therapy, potentially bolstered nanoparticles or plant exosome delivery strategies. In this review, we summarize functions underlying mechanisms cell non-tumor cell-derived progression, with special focus on their roles immunity metabolism. Finally, examine potential application therapeutic targets, highlighting promise clinical use.

Language: Английский

---

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Feb. 8, 2023

RIG-I-like receptors (RLRs) are intracellular pattern recognition that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated 5 (MDA5) laboratory of genetics physiology 2 (LGP2) have distinctive features. These not only recognize RNA intermediates from viruses bacteria, but also interact with endogenous such as the mislocalized mitochondrial RNA, aberrantly reactivated repetitive transposable elements in human genome. Evasion RLRs-mediated response may lead to sustained infection, defective immunity carcinogenesis. Therapeutic targeting provoke anti-infection effects, anticancer sensitize "immune-cold" tumors checkpoint blockade. In this review, we summarize current knowledge signaling discuss rationale for therapeutic cancer. We describe how can be activated by synthetic oncolytic viruses, mimicry radio-chemotherapy, agonists systemically delivered vivo. integration agonism interference CAR-T cells provides new dimensions complement cancer immunotherapy. Moreover, update progress recent clinical trials therapy involving activation modulation. Further studies mechanisms underlying will shed light on development therapeutics. Manipulation represents an opportunity clinically relevant therapy. Addressing challenges field help develop future generations

Language: Английский

---

Cancer stem cells in colorectal cancer: Signaling pathways involved in stemness and therapy resistance

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 182, P. 103920 - 103920

Published: Jan. 23, 2023

Language: Английский

---

Emerging evidence and treatment paradigm of non-small cell lung cancer

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: April 17, 2023

Abstract Research on biomarker-driven therapy and immune check-point blockade in non-small cell lung cancer (NSCLC) is rapidly evolving. The width depth of clinical trials have also dramatically improved an unprecedented speed. personalized treatment paradigm evolved every year. In this review, we summarize the promising agents that shifted for NSCLC patients across all stages, including targeted immunotherapy using checkpoint inhibitors. Based recent evidence, propose algorithms several unsolved issues, which are being explored ongoing trials. results these likely to impact future practice.

Language: Английский

---

Focal adhesion kinase: from biological functions to therapeutic strategies

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

Published: Sept. 25, 2023

Focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, is vital participant in primary cellular functions, such as proliferation, survival, migration, and invasion. In addition, FAK regulates cancer stem cell activities contributes to the formation of tumor microenvironment (TME). Importantly, increased expression activity are strongly associated with unfavorable clinical outcomes metastatic characteristics numerous tumors. vitro vivo studies have demonstrated that modulating by application inhibitors alone or combination treatment regimens could be effective for therapy. Based on these findings, several agents targeting been exploited diverse preclinical models. This article briefly describes structure function FAK, well research progress therapies. We also discuss challenges future directions regarding anti-FAK

Language: Английский

---

Collagen architecture and signaling orchestrate cancer development

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(9), P. 764 - 773

Published: July 1, 2023

Language: Английский

---

cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 17, 2024

Cancer is a complex disease resulting from abnormal cell growth that induced by number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells angiogenesis, plays critical role in progression. Cyclic adenosine monophosphate (cAMP) second messenger has pleiotropic effects on the TME. downstream effectors cAMP include cAMP-dependent protein kinase (PKA), exchange activated (EPAC) ion channels. While can activate PKA or EPAC promote cancer growth, it also inhibit proliferation survival context- type-dependent manner. Tumor-associated stromal cells, such as CAF release cytokines factors either stimulate production within Recent studies have shown targeting signaling TME therapeutic benefits cancer. Small-molecule agents adenylate cyclase been to growth. In addition, cAMP-elevating agents, forskolin, not only induce death, but directly some types. this review, we summarize current understanding biology immunology discuss basis for its context-dependent dual oncogenesis. Understanding precise mechanisms interact will be development effective therapies. Future aimed at investigating cAMP-cancer axis regulation may provide new insights into underlying tumorigenesis lead novel strategies.

Language: Английский

---