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Recent Advances in CAR-Based Solid Tumor Immunotherapy.

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in

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… The interaction between killer cell Ig-like receptors(KIRs) and major histocompatibility complex class I promotes the inhibition of NK cell activation [ 43 ]. NK cells are also involved in antibody-dependent cellular cytotoxicity (ADCC) [ 43 , 99 ]. …

Mechanisms and Applications of Manganese-Based Nanomaterials in Tumor Diagnosis and Therapy.

Tumors are the second most common cause of mortality globally, ranking just below heart disease. With continuous advances in diagnostic technology and treatment approaches, the survival rates of some cancers have increased. Nevertheless, due to the complexity of the mechanisms underlying tumors, cancer remains a serious public health issue that threatens the health of the population globally. Manganese (Mn) is an essential trace element for the human body. Its regulatory role in tumor biology has received much attention in recent years. Developments in nanotechnology have led to the emergence

Последние достижения в области мезенхимической стволовой клеточной терапии для множественных склерозов: клинические виды применения и проблемы.

Множественный склероз (MS), хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризуется воспалением, обезвоживанием и нейродегенерацией, что приводит к различным клиническим проявлениям, таким, как усталость, сенсорное расстройство и когнитивная дисфункция. Текущее фармакологическое лечение направлено прежде всего на иммунную модуляцию, но не позволяет остановить прогрессию заболеваний или полностью обратить на нет повреждения CNS. Лечение стволовыми клетками (MSC) является многообещающей альтернативой, используя иммуномудуляторы, нейрозащиту и регенеративные спосо

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… Changes in the expression and functionality of immunological agents, including T-cell receptor (TCR), immunoglobulin (Ig), major histocompatibility complex (MHC), and cytokines, have been linked to an elevated risk of MS. …

Mitigation and Management of Common Toxicities Associated with the Administration of CAR-T Therapies in Oncology Patients.

Chimeric antigen receptor T-cell (CAR-T) therapies are one of the main approaches among targeted cellular therapies. Despite the potential benefit and durable responses observed in some patients receiving CAR-T therapies, serious and potentially fatal toxicities remain a major challenge. The most common CAR-T-associated toxicities include cytokine release syndrome (CRS), neurotoxicity, cytopenias, and infections. While CRS and neurotoxicity are generally managed with tocilizumab and corticosteroids, respectively, high-grade toxicities can be life-threatening. Close postinfusion monitoring and

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… CAR-T therapy utilizes genetically engineered artificial receptors that recognize tumor cell surface antigens independently of the major histocompatibility complex [ 7 ]. …

What nature has to offer: Opportunities for immuno-oncology.

Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologica

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… Moreover, epigenetic changes are also associated with the expression of antigen-presenting machinery-related genes, such as class I major histocompatibility complex (MHC-I) genes. …

Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.

Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, characterized by rapid proliferation, early metastatic dissemination, and poor long-term survival despite initial sensitivity to therapy. SCLC shares several biologic and therapeutic principles with hematologic malignancies, including lineage state dependence, adaptive resistance through non-genetic plasticity, and emerging susceptibility to antigen-directed immune therapies. Reframing SCLC through this lens provides a conceptual framework for understanding treatment failure and identifying new therapeutic strategie

T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.

T-cell engagers (TCEs) are a rapidly evolving class of cancer immunotherapies that redirect cytotoxic T cells to tumor-associated antigens independently of MHC presentation. This review outlines the development, structural formats, and therapeutic potential of various TCE platforms, including bispecific (BiTEs) and trispecific T-cell engagers (TriTEs), dual affinity re-targeting (DART), and other emerging formats. We also highlight the clinical success in treating hematologic malignancies as demonstrated by agents such as blinatumomab and teclistamab. We also discussed the ongoing challenges i

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… This complex is a multimeric structure composed of a variable αβ heterodimer (TCRα/TCRβ), which recognizes the peptide–major histocompatibility complex (MHC), and three invariant CD3 dimers, CD3γϵ, CD3δϵ, and CD3ζζ, arranged in a fixed stoichiometry. …

CAR T-клеточная терапия для неврологических расстройств: научное обоснование и механистические исследования.

Разработка и успешное клиническое применение инженерных Т-клеток, содержащих синтетические химериковые антигенные рецепторы (CARs), является важной вехой в лечении рака. Этот подход оптимизирует физиологическую активацию в виво Т-клеток в отношении конкретных целевых антигенов, выраженных на определенных поднаборах клеток, с целью их глубокого и устойчивого истощения. Значительный прогресс был достигнут в реорганизации зданий ЦАР-Т-клеток в целях повышения безопасности, терапевтической эффективности и доступности. Усилия также были сосредоточены на рационализации обрабатывающей промышленности

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… As another key distinction from the Ig on the surface of B-cells, which can bind free-floating antigens in their native form, T cells rely on their TCR to recognize antigens only when they are processed into peptide fragments and presented by major histocompatibility complex (MHC) molecules on the surface …

CAR-T cell therapy in Multiple Myeloma: current status and future challenges.

The treatment of multiple myeloma has changed dramatically in recent years, with huge strides forward made in the field. Chimeric antigen receptor T-cell therapy targeting the B cell maturation antigen (BCMA) is now widely approved in relapsed refractory patients and is moving into earlier treatment lines. In this review, we discuss the evidence underpinning current regulatory approvals and consider mechanisms through which CAR-T cell efficacy could be improved. These include tackling BCMA-loss, harnessing the immunosuppressive tumour microenvironment, manufacturing concerns including the pote

Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence.

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety

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… Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scandinavian Journal of Immunology. 2003;57(1):11–20. doi: 10.1046/j.1365-3083.2003.01176.x. 87. Liang Z.-X., Sun J. …

Clinical application of cytokine-induced killer cells in cancer immunotherapy.

Cytokine-induced killer (CIK) cells exhibit potent antitumor activity with reduced dependence on strict MHC compatibility, mediated by a combination of T-cell receptor (TCR)-dependent recognition and natural killer (NK)-like, MHC-unrestricted cytotoxicity. This narrative review synthesizes evidence from clinical trial evaluations, including 48 published studies. We examine strategies to enhance CIK function, such as engineering, combination with checkpoint inhibitors, and co-administration with dendritic cells. CIK cell therapy effectively reduces post-treatment recurrence in the adjuvant sett

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… This major histocompatibility complex (MHC)-unrestricted killing, combined with their excellent safety profile characterized by minimal toxicity, carves out a distinct and clinically valuable niche for CIK cells in the competitive landscape of ACTs, which includes complex and toxic options such as chimeric …

Waldenström macroglobulinemia: clinical and immunological aspects, natural history, cell of origin, and emerging mouse models.

Waldenström macroglobulinemia (WM) is a rare and currently incurable neoplasm of IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function

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… These results indicate that only those pP-7-carrying individuals are at elevated risk of developing WM that have the requisite MHC (major histocompatibility complex) class II haplotype for cognate interaction of antigenic pP-7 peptides and CD4 + T cells. …

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identify

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… Fig. 2 Examples of tumour resistance mechanisms. 1: Tolerogenic dendritic cells (TLDCs) are characterized by weak capture of cancer antigens, low expression of major histocompatibility complex (MHC) and costimulatory molecules, high expression of inhibitory molecules and regulatory cytokines (FAS, PDL …

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

Иммуномодулирующие свойства месенхимальных стволовых клеток и их внеклеточных везиков: потенциальные клинические применения в аутоиммунных заболеваниях.

Мезенхимальные стволовые клетки (МСЦ)/мезенхимические стромальные клетки и их внеклеточные везикли (ЭМ), в частности экзосомы, появились в качестве терапевтических кандидатов в регенеративной медицине в силу их многопотенции, низкой иммуногенности и обширных иммунодуляторных свойств. В настоящем описательном обзоре содержится сводная информация об иммуномодуляции МСЦ- и МСЦ-В и о ее потенциале в плане перевода на другие языки. four основные аутоиммунные заболевания: множественный склероз (МС), тип 1 - сахарный диабет (T1D), системный волшебный эриматоз (SLE) и ревматоидный артрит (RA).Механист

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… Although allogeneic MSCs were initially considered immune privileged due to their low expression of major histocompatibility complex (MHC) and co-stimulatory molecules, they can be recognized by the host immune system and have been shown to elicit anti-donor immune responses involving dendritic cells …

Cancer immunotherapies: A hope for the uncurable?

The use of cancer immunotherapies is not novel but has been used over the decades in the clinic. Only recently have we found the true potential of stimulating an anti-tumor response after the breakthrough of checkpoint inhibitors. Cancer immunotherapies have become the first line treatment for many malignancies at various stages. Nevertheless, the clinical results in terms of overall survival and progression free survival were not as anticipated. Majority of cancer patients do not respond to immunotherapies and the reasons differ. Hence, further improvements for cancer immunotherapies are cruc

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… These receptors associate with CD3 in the surface membrane and recognize major histocompatibility complexes (MHC) loaded with an antigen which induces activation and killing of the tumor cell ( Harris and Kranz, 2016 ; June et al., 2018 ). …

Биотипные антитела в гематологовых злодеях: атакуют фронтлайн.

С тех пор, как Блинатумомаб утвердился в качестве первого биконкретного антитела (BsAb) в лечении рака, эти иммунодуляторные агенты добились значительного успеха в лимфоидных малигнатах. Через десять лет после предварительного одобрения в рентгеновских условиях блинатумомаб стал частью первой линии индуктивной терапии для пациентов с острой лимфоболической лейкемией (B-ALL). Теперь, six Кроме того, БСАБ имеют разрешение УЛХ на обработку лимфомы В-клеток, не относящихся к Ходжкину, и множественной миеломы (ММ), что позволяет добиться высоких показателей ответов в других сценариях. В лимфоме, эп

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… These cells express a range of inhibitory and activating receptors; for example, inhibitory receptors bind major histocompatibility complex class I (MHC Class I) molecules to limit autoimmune responses, while the loss of MHC expression on tumor cells can trigger NK cell-mediated killing. …

Genomic innovations in cancer prevention, diagnosis, prognosis and precision therapeutics.

Cancer research has undergone a transformative change with the advent of high-throughput genomic technologies. Advances in next-generation sequencing accelerated the identification of somatic and germline alterations that drive tumorigenesis enabling the transition from traditional histology-based cancer classification to molecularly informed precision oncology. Large-scale sequencing initiatives and clinical genomic profiling facilitated the development of companion diagnostic assays and targeted therapies. Beyond targeted therapies, genomic innovations have also catalyzed the emergence of no

Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy.

Upfront high-dose therapy with melphalan (HDM) followed by autologous stem cell transplantation (ASCT) has established itself as a core treatment for newly diagnosed multiple myeloma (NDMM) patients in the past 30 years. Induction therapy, HDM-ASCT, and subsequent consolidation and maintenance therapy comprise the current fundamental framework for MM treatment. The introduction of anti-CD38 monoclonal antibodies such as daratumumab and isatuximab has changed the treatment paradigm for transplant-eligible NDMM patients in that quadruplets have become the new standard induction therapy. The trea

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… This cellular interaction leads to the activation of T cells in the immune system independently of antigen presentation on the major histocompatibility complex (MHC) class 1, which releases substances, including granzyme B and perforins, subsequently initiating the apoptotic cascade within the neoplastic …

Present and Future Role of Immune Targets in Acute Myeloid Leukemia.

It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on AML cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets

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… Figure 1 Schematic representation of the cellular mechanisms of anti-tumor surveillance escape in AML. ( A ) Cellular cross-talks: leukemic stem cells (LSCs) and T cells direct interaction, through major histocompatibility complex (MHC) and over-expressed immune checkpoint ligands (PD-L1), causes functional …