Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10
Published: Sept. 11, 2024
EphA2 is a tyrosine kinase receptor and considered promising target in cancer. Different approaches are used to receptor, lot of preclinical data demonstrate the potential exploitation this clinical oncology for diagnosis cancer therapy, including immunotherapy.
Language: Английский
JAMA Neurology, Journal Year: 2024, Volume and Issue: 82(1), P. 93 - 93
Published: Nov. 25, 2024
Importance Advancements in molecular engineering have facilitated the creation of engineered T cells that express synthetic receptors, termed chimeric antigen receptors (CARs). This is promising not only cancer treatment but also addressing a spectrum other conditions. review provides comprehensive overview current approaches and future potential CAR T-cell therapy field neurology, particularly for primary brain tumors autoimmune neurological disorders. Observations glioblastoma promising; however, first-in-human trials did yield significant success or showed limited subset patients. To date, efficacy therapies has been demonstrated animal models multiple sclerosis, larger human studies to corroborate remain pending. patients with relapsed refractory aquaporin 4–immunoglobulin G–seropositive neuromyelitis optica Further patient populations are needed confirm these results. Success was reported cases generalized myasthenia gravis using cells. Chimeric autoantibody receptor cells, representing modified form directed against autoreactive B secreting autoantibodies, were used selectively target anti– N -methyl- d -aspartate under vitro vivo conditions, providing basis application types encephalitis associated neuronal glial antibodies. Conclusions Relevance herald new era therapeutic landscape While their solid tumors, such as glioblastoma, universally yielded robust success, emerging innovative strategies show promise, there optimism effectiveness certain
Language: Английский
Citations
6
Cancer Letters, Journal Year: 2024, Volume and Issue: 600, P. 217185 - 217185
Published: Aug. 12, 2024
Glioblastoma, a highly malignant intracranial tumor, has acquired slow progress in treatment. Previous clinical trials involving targeted therapy and immune checkpoint inhibitors have shown no significant benefits treating glioblastoma. This ineffectiveness is largely due to the complex immunosuppressive environment of Glioblastoma cells exhibit low immunogenicity strong heterogeneity microenvironment replete with inhibitory cytokines, numerous cells, insufficient effective T cells. Fortunately, recent Phase I CART for glioblastoma confirmed its safety, small subset patients achieving survival benefits. However, continues face challenges, including blood-brain barrier obstruction, antigen loss, an tumor (TME). article provides detailed examination glioblastoma's microenvironment, both from intrinsic extrinsic cell factors, reviews current basic research on multi-targets treatment, concludes by outlining key challenges using therapy.
Language: Английский
Citations
5
Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)
Published: Oct. 4, 2024
Abstract Glioblastomas (GBMs) are the most common and aggressive malignant brain tumors, presenting significant challenges for treatment due to their invasive nature localization in critical regions. Standard includes surgical resection followed by radiation adjuvant chemotherapy with temozolomide (TMZ). Recent advances immunotherapy, including use of mRNA vaccines, offer promising alternatives. This review focuses on emerging vaccines GBM treatment. We summarize recent advancements, evaluate current obstacles, discuss notable successes this field. Our analysis highlights that while have shown potential, is still experimental. Ongoing research clinical trials essential fully understand therapeutic potential. Future developments vaccine technology insights into GBM-specific immune responses may lead more targeted effective treatments. Despite promise, further crucial validate optimize effectiveness combating GBM. Graphical
Language: Английский
Citations
5
Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)
Published: Nov. 6, 2024
Abstract The application of chimeric antigen receptor T-cell therapy in central nervous system tumors has significantly advanced; however, challenges pertaining to the blood-brain barrier, immunosuppressive microenvironment, and antigenic heterogeneity continue be encountered, unlike its success hematological malignancies such as acute lymphoblastic leukemia diffuse large B-cell lymphomas. This review examined research progress gliomas, medulloblastomas, lymphohematopoietic system, focusing on T-cells targeting antigens EGFRvIII, HER2, B7H3, GD2, CD19 preclinical clinical studies. It synthesized current findings offer valuable insights for future therapeutic strategies advance development this modality domain.
Language: Английский
Citations
4
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: March 20, 2025
Various challenges, including tumor heterogeneity and inadequate T cell infiltration, impede the progress of chimeric antigen receptor (CAR-T) therapy for glioblastoma (GBM). To address these obstacles, a multiple step strategy is designed. Initially, literature review bioinformatics analysis to screen set antigens that are heterogeneously expressed in GBM, which designated as target-bank, leveraged. Then, according multiplex immunohistochemistry results each patient's sample, personalized panel based on principle most cancer cells tissues can be covered from target-bank selected. target antigens, Vδ1 chosen CAR vehicles because its high tissue infiltration off-the-shelf properties, an optimized protocol engineering CAR-Vδ1 with purity cytotoxicity, low exhaustion, cytokine release developed. Next, specific cocktail GBM organoids directly derived same tested. The term "prof" coined describe approach using precise rational combination organoid-based evaluation, fitness cells. It may accelerate development effective CAR-T drugs heterogeneous solid tumors.
Language: Английский
Citations
0
Exploration of Targeted Anti-tumor Therapy, Journal Year: 2025, Volume and Issue: 6
Published: April 27, 2025
Neoantigen-based immunotherapy has emerged as a transformative approach in cancer treatment, offering precision medicine strategies that target tumor-specific antigens derived from genetic, transcriptomic, and proteomic alterations unique to cells. These neoantigens serve highly specific targets for personalized therapies, promising more effective tailored treatments. The aim of this article is explore the advances neoantigen-based highlighting successful treatments such vaccines, tumor-infiltrating lymphocyte (TIL) therapy, T-cell receptor-engineered T cells therapy (TCR-T), chimeric antigen receptor (CAR-T), particularly types like glioblastoma (GBM). Advances technologies next-generation sequencing, RNA-based platforms, CRISPR gene editing have accelerated identification validation neoantigens, moving them closer clinical application. Despite results, challenges tumor heterogeneity, immune evasion, resistance mechanisms persist. integration AI-driven tools multi-omic data refined neoantigen discovery, while combination therapies are being developed address issues suppression scalability. Additionally, discusses ongoing development immunotherapies targeting mutations, emphasizing need continued collaboration between computational experimental approaches. Ultimately, cutting-edge research holds potential revolutionize care, hope targeted
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: May 21, 2025
Human epidermal growth factor receptor 2 (HER2) is highly expressed in various solid tumors, and its abnormal activation closely associated with poor tumor prognosis, establishing it as a prominent target contemporary research. The successful clinical treatment of multiple HER2-positive tumors HER2 antibodies has prompted researchers to design chimeric antigen T (CAR-T) cells targeting for immunotherapy. To date, the development CAR structures progressed fifth generation, most HER2-CAR-T cell being modified based on second-generation architecture. This review will delineate structure cytotoxic mechanism cells, elucidate difficulties optimization strategies therapy, summarize recent applications advancements.
Language: Английский
Citations
0
Chaos An Interdisciplinary Journal of Nonlinear Science, Journal Year: 2025, Volume and Issue: 35(6)
Published: June 1, 2025
Malignant gliomas (MGs) are among the most aggressive primary brain tumors, characterized by a high degree of resistance to therapy and poor prognosis. In this work, we develop mathematical model investigate dynamics MG under combined effects chemotherapy chimeric antigen receptor cell therapy. The proposed is five-dimensional dynamical system incorporating impulsive inputs that correspond clinical administration immunotherapy. We demonstrate non-negativity solutions for non-negative initial conditions, ensuring biological relevance model. show if apply both therapies only once, trajectories attracted an invariant surface corresponding tumor carrying capacity. Conversely, constant treatments, identify parameter ranges in which eradication achievable. Furthermore, numerically study various treatment combinations determine optimal protocols at population level. To end, generate cohort 104 virtual patients with parameters sampled uniformly within clinically relevant carry out silico trials. Our findings indicate growth rate, efficacy, tumor-induced immunosuppression key determinants survival outcomes. believe our results provide new theoretical insights into optimization offer framework refining design trials therapies.
Language: Английский
Citations
0
Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1086 - 1086
Published: June 22, 2024
The abnormal growth of oligodendrocyte precursor cells (OPCs) significantly contributes to the progression glioblastoma tumors. Hence, molecules that block OPC may be therapeutic importance in treating gliomas. 2-Methoxyestradiol (2ME), an endogenous tubulin-interacting metabolite estradiol, is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions, it undergoing phase II clinical trials. We hypothesize 2ME prevent glioma by targeting growth. Here, we tested this hypothesis assessing impact line, “Oli-neu”, dissected underlying mechanism(s). Treatment with inhibited a concentration-dependent manner, accompanied significant upregulation expression p21 p27, which are negative cell-cycle regulators. Moreover, treatment altered morphology from multi-arm processes rounded cells. At concentrations 1uM greater, induced apoptosis, increased expressions caspase 3, PARP, caspase-7 fragments, externalized phosphatidylserine staining/APOPercentage, mitochondrial activity. Flow cytometry microscopic analysis demonstrated triggers endoreduplication fashion. Importantly, cyclin E, JNK1/2, p53 expression, as well fusion, key mechanisms driving whole-genome duplication. inhibition pifithrin-α rescued 2ME-induced endoreduplication. pro-apoptotic actions were survivin, A, Cyclin B, D2, ppRB. Similar inhibitory, apoptotic, effects observed CG4 Taken together, our findings provide evidence not only inhibits but also activates OPCs into survival (fight or flight) mode, leading This inherent characteristic may, part, responsible for drug resistance gliomas, many drugs. fate after depend status individual Combining tubulin-interfering drugs such inhibit help OPC/glioma limit resistance.
Language: Английский
Citations
2
Cancer Research Communications, Journal Year: 2024, Volume and Issue: 4(9), P. 2514 - 2524
Published: Sept. 1, 2024
Cancer immunotherapy using immune checkpoint inhibitors and its combination with other anticancer therapies has emerged as a new standard of care because the encouraging therapeutic effects in various solid cancers. Nonetheless, glioblastoma pancreatic cancer remain resistant to represent intractable cancers poorest prognosis. We investigated next-generation chimeric antigen receptor (CAR) T cells producing IL7 chemokine (C-C motif) ligand 19 (CCL19; referred 7 × CAR-T) these Cytotoxic activities CAR-T were evaluated vitro vivo, model EGFR variant III (EGFRvIII)-positive anti-EGFRvIII generated from healthy donor peripheral blood mononuclear (PBMC), or HER2-positive organoids anti-HER2 same patient's PBMC. Anti-EGFRvIII exhibited cytotoxic activity specific EGFRvIII-positive tumor, induced complete rejection massive T-cell infiltration tumor cell death tissues, consequently prolonged mouse survival. Anti-HER2 demonstrated potent against autologous along Our results suggest that could become option for cancer. To best our knowledge, this is first study demonstrate efficacy an patient-derived PBMC, which unwanted allogeneic responses are fully excluded.
Language: Английский
Citations
2