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Immune-based cancer therapies: mechanistic insights, clinical progress, and future directions.

The field of cancer immunotherapy has evolved rapidly, offering new treatment paradigms by harnessing the body's own immune system to target and destroy malignancies. Various immunotherapeutic approaches, including immune checkpoint inhibitors, CAR-T cell therapy, cancer vaccines, cytokine therapies, and oncolytic viruses, have shown significant promise in treating different cancer types. This review provides a comprehensive examination of the historical development and recent advances in cancer immunotherapy. We discuss the mechanisms of action of key immunotherapeutic modalities, along with

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… The production of exosomes by dendritic cells with cancer antigens and functional major histocompatibility complexes (MHCs) was reported by Zitvogel et al. These findings revealed that these exosomes could initiate the neutralization of tumors by cytotoxic T lymphocytes (CTLs) [ 191 ]. …

Challenges and innovations in CAR-T cell therapy: a comprehensive analysis.

Recent years have seen a marked increase in research on chimeric antigen receptor T (CAR-T) cells, with specific relevance to the treatment of hematological malignancies. Here, the structural principles, iterative processes, and target selection of CAR-T cells for therapeutic applications are described in detail, as well as the challenges faced in the treatment of solid tumors and hematological malignancies. These challenges include insufficient infiltration of cells, off-target effects, cytokine release syndrome, and tumor lysis syndrome. In addition, directions in the iterative development o

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… The key difference between CAR-T cells and TCR T cells is that the former do not rely on immunogenic processing and peptide presentation by major histocompatibility complex (MHC) receptors, thus increasing the applicability of CAR-T to different patients ( 7 , 8 ). …

CBD promotes antitumor activity by modulating tumor immune microenvironment in HPV associated head and neck squamous cell carcinoma.

IntroductionMarijuana use is associated with HPV-positive head and neck squamous cell carcinoma (HNSCC). However, cannabinoid use continues to increase in the US general population for recreational purposes as well as in cancer patients for palliative care. In this study, we explored the role of cannabidiol (CBD) in promoting anti-tumor activity by modulating immune response in HPV-positive HNSCC by using pre-clinical models.MethodsThe anti-proliferative effect of CBD on HPV-positive HNSCC cells was evaluated through BrdU, apoptosis and migration analyses, followed by western blot analysis to

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… CD4+T cells bind with the major histocompatibility complex (MHC) class II and help increase cytokine production by T helper cells ( 70 ) and the CD8+T cells interact with MHC class I molecules to show their immune defense towards pathogens, viruses, and bacteria, and also help the immune system to recognize …

Cell-based immunotherapy of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary glial brain tumor. It has an unfavorable prognosis and relatively ineffective treatment protocols, with the median survival of patients being ~15 months. Tumor resistance to treatment is associated with its cancer stem cells (CSCs). At present, there is no medication or technologies that have the ability to completely eradicate CSCs, and immunotherapy (IT) is only able to prolong the patient's life. The present review aimed to investigate systemic solutions for issues associated with immunosuppression, such as ineffective

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… TGF-β inhibits inflammation, triggers ECM repair, increases the interaction between cancer cells and the ECM ( 53 ), creates a niche for cancer cells ( 54 ), hinders T cell proliferation, suppresses antigen presentation by macrophages, inhibits the expression of major histocompatibility complex (MHC) …

Cytokine-Induced Killer Cells: A Unique Platform for Adoptive Cell Immunotherapy after Allogeneic Hematopoietic Stem Cell Transplantation.

BackgroundImmunotherapies in general, and cellular immunotherapies, in particular are becoming increasingly integrated into current personalized cancer treatment, though still facing some obstacles in the allogeneic hematopoietic stem cell transplantation (HSCT) setting.SummaryThe concept of isolating immune effector cells, expanding their numbers, enhancing their anticancer capabilities by modifying them without increasing their alloreactive potential is the mainstay of adoptive cellular immunotherapy after allogeneic HSCT. In this context, cytokine-induced killer (CIK) cells, a polyfunctiona

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… The efficacy of CIK cells generated by this protocol, in general, was due to the enrichment of immune cells, namely, T cells, NK cells, and, in particular, T-NK cells, which showed natural non-major histocompatibility complex (MHC)-restricted cytotoxicity against various cancers, particularly through …

Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs.

Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex(GM-CSF)]), is almost complete, wi

mRNA vaccine in cancer therapy: Current advance and future outlook.

Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisitio

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… Exosomes are most used in cancer vaccine development, which exerts dendritic cell‐released major histocompatibility complex (MHC) class I/peptide complexes for efficient CD8 + T cell priming to suppress tumour growth. 182 , 183 Microneedles, both solid microneedle patches and hollow microneedles for …

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Ne

Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

With recent advances, chimeric antigen receptor (CAR) immunotherapy has become a promising modality for patients with refractory cancer diseases. The successful results of CAR T cell therapy in relapsed and refractory B-cell malignancies shifted the paradigm of cancer immunotherapy by awakening the scientific, clinical, and commercial interest in translating this technology for the treatment of solid cancers. This review elaborates on fundamental principles of CAR T cell therapy (development of CAR construct, challenges of CAR T cell therapy) and its application on solid tumors as well as CAR

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… The direct binding of CAR to antigen induces a competent activation signal, proliferation, and cytokine production independent of major histocompatibility complex (MHC) with extended applicability to multiple types of cancer [ 41 – 43 ]. …

Revisiting potential value of antitumor drugs in the treatment of COVID-19.

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of d

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… The phosphoinositide kinase PIKfyve promotes cathepsin-S-mediated major histocompatibility complex class II antigen presentation. iScience. 2019;11:160–77. doi: 10.1016/j.isci.2018.12.015. 48. Wu CT, Lidsky PV, Xiao Y, Lee IT, Cheng R, Nakayama T, et al. …

Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.

Pharmaceutical companies keep producing novel drugs and drug treatments for improving the life of every sick individual, most often following a pattern; a specific drug for a specific condition. Evidence suggests that different medications can have a positive effect on different pathological conditions. The full potential of existing therapies can be revealed through drug repurposing-also referred to as drug repositioning, reprofiling, or re-tasking-which involves identifying new therapeutic uses for approved or investigational drugs beyond their original indications. One significant target in

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential t

Chimeric Antigen Receptor T Cells as Living Therapeutics Targeting Senescence and Age-Related Diseases.

The aging of the global population exacerbates the burden of age-related diseases; however, therapies that can intervene in fundamental aging processes are lacking. Senescent cells drive chronic inflammation and multitissue dysfunction through the secretion of proinflammatory and profibrotic senescence-associated secretory phenotype cells, making them emerging therapeutic targets. Although first-generation senolytic drugs have entered clinical trials, they face limitations such as insufficient targeting specificity and transient efficacy. The success of chimeric antigen receptor T cell (CAR T

Total Body Irradiation in Haematopoietic Stem Cell Transplantation for Paediatric Acute Lymphoblastic Leukaemia: Review of the Literature and Future Directions.

Total body irradiation (TBI) has been a pivotal component of the conditioning regimen for allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) in very-high-risk acute lymphoblastic leukaemia (ALL) for decades, especially in children and young adults. The myeloablative conditioning regimen has two aims: (1) to eradicate leukaemic cells, and (2) to prevent rejection of the graft through suppression of the recipient's immune system. Radiotherapy has the advantage of achieving an adequate dose effect in sanctuary sites and in areas with poor blood supply. However, radiotherapy

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… . | ( 171 – 173 ) Development of restrictive/obstructive lung disease after HSCT is multifactorial, including the transplant regimen, diagnosis, donor major histocompatibility complex mismatch, chronic GvHD, and time after transplant. | Consequence for fractionated TBI | Paediatric oncology radiotherapy …

Research Progress of NK Cells in Glioblastoma Treatment.

NK cells are a type of antitumor immune cell with promising clinical application, following T cells. The activity of NK cells is primarily regulated by their surface receptors and immune microenvironment. In gliomas, the tumor microenvironment exerts a strong immunosuppressive effect, which significantly reduces the clinical efficacy of NK cell immunotherapy. Therefore, this review aims to discuss the latest research on the role of NK cells in glioma immunotherapy, focusing on aspects such as NK cell development, function, and localization. It summarizes information on the compounds, monoclona

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… NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis . J Exp Med . 1998 ; 187 ( 12 ): 2065 – 2072 . doi: 10.1084/jem.187.12.2065 9625766 PMC2212362 17. …

Novel Treatment Strategies Utilizing Immune Reactions against Chronic Myelogenous Leukemia Stem Cells.

Introduction of tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myelogenous leukemia (CML), and treatment-free remission (TFR) is now a treatment goal. However, about half of the patients experience molecular relapse after cessation of TKIs, suggesting that leukemic stem cells (LSCs) are resistant to TKIs. Eradication of the remaining LSCs using immunotherapies including interferon-alpha, vaccinations, CAR-T cells, and other drugs would be a key strategy to achieve TFR.

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… Tarafdar et al. found that IL-4 gene expression was upregulated in CML-LSCs, which suppresses class II transactivator (CIITA) transcription and subsequently expression of major histocompatibility complex-II (MHC-II) in CML-LSCs compared to normal hematopoietic stem cells (HSCs) [ 25 ]. …

Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies.

Ocular malignancies, particularly uveal and conjunctival melanoma, exemplify tumors that evolve within one of the body's most immunologically constrained ecosystems, the eye's immune-privileged microenvironment. The limited success of PD-1/PD-L1 and CTLA-4 blockade in these cancers underscores the need to move beyond linear checkpoint inhibition toward multidimensional immune engineering. Through the confluence of synthetic bio-nanotechnology, AI-guided immunogenomics, and spatial immunomics, this review reframes ocular immunotherapy and redefines how tolerance and immunity might be programmat

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… Conversely, over 90% of the human proteome is located intracellularly, rendering it unattainable by traditional antibody-based methods and highlighting the necessity for alternate ways to address intracellular targets. 130 , 131 The appearance of intracellular antigens on major histocompatibility complex …

Терапия сотовой связи для руматоидного артрита.

Химерическая антигенная рецепторная (CAR) клеточная терапия Т произвела революцию в лечении лейкемии, лимфомы и множественных миеломы, реанимировав на поверхности этих клеток антигены CD19 и BCMA. В последнее время появляется все больше свидетельств того, что эти клеточные методы лечения могут также быть направлены против аутоиммунных заболеваний, включая системный волчаньий эритематос, системный склероз, расстройство спектрального спектра нейромиелита, миастения гравис, идиопатический воспалительный миосит, множественный склероз и ревматоидный артрит. На сегодняшний день ten Пациенты с ревмат

Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.

Since the United States Food and Drug Administration approved the first immune checkpoint inhibitor ipilimumab for metastatic melanoma in 2011, ICIs have been approved for a range of cancers and significantly improving treatment outcomes. However, the objective response rate of ICI monotherapy remains modest (10-40%), with clinical benefit observed in only 15-20% of patients. The limited efficacy of ICIs in many patients is often attributed to poorly immunogenic ("cold") tumors. Radiotherapy and chemotherapy exhibit immunomodulatory properties that can enhance tumor immunogenicity. These effec

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… It includes: (1) The upregulation of new antigens, an increase in TAAs, and enhanced antigen presentation by APCs. (2) The occurrence of ICD, the release of DAMPs, and their interaction with antigen‐presenting cells. (3) The upregulation of major histocompatibility complex (MHC) class I molecules and …

T-клеток, перенаправляющих терапию на рецидив миеломы.

В последние годы использование иммуномодуляционных препаратов, протеиозных ингибиторов и CD38, направленных против моноклонных антител, привело к значительному улучшению общих результатов пациентов с множественной миеломой. Несмотря на эти достижения, рецидивы остаются обычным явлением, и до недавнего времени прогнозы таких пациентов охранялись. Одобрение T-клеток химерика антигенного рецептора (CAR) и Т-комплексов (TCE) значительно повысило выживаемость этих пациентов с тройной и пента-классовой рефракторной болезнью. В настоящем документе рассматриваются клинические результаты, связанные с э