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Harnessing CAR-Extracellular Vesicles for Next-Generation Cancer Immunotherapy.

Cancer immunotherapy has experienced substantial progress in recent years, particularly with the advancement of chimeric antigen receptor (CAR) technology, which enables immune cells to selectively target tumor-associated antigens. CARs, now in their fifth generation, are engineered by combining monoclonal antibody fragments with signaling and co-stimulatory domains and have been successfully applied to T cell, natural killer (NK) cell, and macrophage-based therapies. Notable clinical successes, such as tisagenlecleucel and lisocabtagene maraleucel underscore the therapeutic potential of CAR-T

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… Although CAR-NK cells exhibit a relatively reduced susceptibility to classical checkpoint inhibition, their anti-tumor activity is nonetheless constrained by tumor-mediated modulation of ligand expression, specifically the downregulation of activating ligands such as major histocompatibility complex … histocompatibility complex MICA MHC class I chain-related protein A MICB MHC class I chain-related protein B MM Multiple myeloma MMC Multimodal chromatography MSC Mesenchymal stem cell NK Natural killer PD-1 Programmed cell death protein 1 PDAC Pancreatic ductal adenocarcinoma PD-L1 Programmed death-ligand …

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

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… histocompatibility complex; APC, Antigen presenting cell; CAR, Chimeric antigen receptor; IL13Rα2, interleukin 13 receptor subunit alpha 2; HER2, human epidermal growth factor receptor 2; mbMMP2, membrane-bound metalloproteinases 2; B7-H3, B7 homolog 3; EphA2, Ephrin type-A receptor 2; EGFR, Epidermal … It involves the inducible expression of a chimeric antigen receptor (CAR), engineered to target a specific antigen of interest on autologous T cells, hence bypassing the need for antigen presentation by Major Histocompatibility Complex (MHC) otherwise required for the activation of endogenous T cells …

Биоинженерная клеточная терапия для педиатрических твердых опухолей: неудовлетворенные потребности и комплексный подход к измерению.

Твердые педиатрические опухоли по-прежнему представляют собой серьезную терапевтическую проблему, при этом успехи в области выживания отстают от тех, которые были достигнуты в области педиатрических гематологов. Хотя в рамках традиционных подходов основное внимание уделяется увеличению доз и интенсификации системной терапии в целях повышения выживаемости, эта стратегия зачастую ограничивается значительной краткосрочной и долгосрочной заболеваемостью в результате интенсивной мультимодальной обработки. Поскольку у детей есть органы и десятилетия жизни впереди, терапевтические стратегии должны ур

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… This engineered receptor bypasses conventional major histocompatibility complex-restricted antigen presentation, enabling potent, antigen-specific killing upon engagement of the target [ 24 ]. …

Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after autotransplant.

Posttransplant vaccination targeting residual disease is an immunotherapeutic strategy to improve antigen-specific immune responses and prolong disease-free survival after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We conducted a phase 1 vaccine trial to determine the safety, toxicity, and immunogenicity of autologous Langerhans-type dendritic cells (LCs) electroporated with CT7, MAGE-A3, and Wilms tumor 1 (WT1) messenger RNA (mRNA), after ASCT for MM. Ten patients received a priming immunization plus 2 boosters at 12, 30, and 90 days, respectively, after ASCT. Vacc

Skin Hypopigmentation in Hematology Disorders.

Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores

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… Specific Cytotoxic T Lymphocyte Responses against Melan-A/MART1, Tyrosinase and Gp100 in Vitiligo by the Use of Major Histocompatibility Complex/Peptide Tetramers: The Role of Cellular Immunity in the Etiopathogenesis of Vitiligo J. Investig. …

Safety Strategies of Genetically Engineered T Cells in Cancer Immunotherapy.

T-cell therapy using genetically engineered T cells modified with either T cell receptor or chimeric antigen receptor holds great promise for cancer immunotherapy. The concerns about its toxicities still remain despite recent successes in clinical trials. Temporal and spatial control of the engineered therapeutic T cells may improve the safety profile of these treatment regimens. To achieve these goals, numerous approaches have been tested and utilized including the incorporation of a suicide gene, the switch-mediated activation, the combinatorial antigen recognition, etc. This review will sum

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… Genetically modified T cells are generated by transferring α and β chains of TCRs derived from tumor reactive T cell clones, thus rendering T cells antigenic specificity through recognition of the antigens presented by major histocompatibility complex (MHC) molecules on the target cells. …

CAR-T in relapsed refractory high-grade glioma and glioblastoma - who, what, when and how?

Recurrent high-grade gliomas have a dismal prognosis. This review article aimed to explore and help answer the questions about which group of patients would benefit from chimeric antigen receptor therapy (CAR-T) cell therapy in this setting, the timing of intervention and the therapeutic efficacy. CAR-T cell therapy involves the extraction of T-cells from patients, genetic modification of these cells to express chimeric antigen receptors on their cell surface, which are selectively targeted towards tumour-expressed antigens and a procedure of immune-depletion followed by re-introducing these e

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… CAR-T innovation enables us to, theoretically, do systemic targeted elimination of cancer cells in a major histocompatibility complex independent manner. …

Keyword Index for Volume 109

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Targeting HLA-E in Lung Cancer: The Therapeutic Potential of IRF5-Engineered M1-Macrophage-Derived Exosomes.

Immunotherapy is a pivotal approach in the treatment of lung cancer. Although HLA-E is a potential target for tumor immunotherapy, its role in lung cancer remains unclear. Previous studies have identified the transcription factor IRF5 as a characteristic gene of M1-like macrophages, highlighting its crucial role in promoting antitumor immune responses. In this study, we developed an engineered M1-like macrophage exosomes expressing IRF5 (IRF5 M1-exos) and demonstrated their ability to inhibit proliferation, migration, and invasion of lung cancer cells. Moreover, our experiments using a nude mo

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… HLA‐E is a nonclassical MHC (major histocompatibility complex) Class I molecule that plays a crucial role in immune system regulation. …

Targeting Proteasomes in Cancer and Infectious Disease: A Parallel Strategy to Treat Malignancies and Microbes.

Essential core pathways of cellular biology are preserved throughout evolution, highlighting the importance of these pathways for both bacteria and human cancer cells alike. Cell viability requires a proper balance between protein synthesis and degradation in order to maintain integrity of the proteome. Proteasomes are highly intricate, tightly regulated multisubunit complexes that are critical to achieve protein homeostasis (proteostasis) through the selective degradation of misfolded, redundant and damaged proteins. Proteasomes function as the catalytic core of the ubiquitin-proteasome pathw

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… Proteasomal hydrolysis of intracellular proteins also generates peptides that function as antigens bound to the major histocompatibility complex (MHC) class I molecule. …

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu

NK cell based immunotherapy against oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck cancers, presents significant challenges due to its aggressive feature and limited therapeutic efficacy of conventional treatments. In response to these challenges, Natural Killer (NK) cells, a vital component of the innate immune system, are being explored for their therapeutic potential in OSCC due to their inherent ability to target and eliminate cancer cells without prior sensitization. This review uniquely focuses on the evolving role of NK cells specifically in OSCC, incorporating recent advancements in CAR-NK cell eng

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… Unlike T cells, NK cells are not restricted by major histocompatibility complex (MHC) molecules. Their activation is controlled through a balance of surface activating and inhibitory receptors. … Furthermore, NK cells’ mechanisms of action do not rely on antigen presentation by Major Histocompatibility Complex (MHC) molecules, which are often downregulated in OSCC cells to evade immune detection. …

Нацеливаюсь на иммунологический синапс в нескольких миэломах.

Иммунологический синапс, высокоорганизованный соединитель клеток, является важной основой для эффективного убийства раковых клеток с помощью Т. Однако в миеломе терапевтическое сопротивление отражает множество взаимодействующих слоев, включая синаптическое нарушение, клональную эволюцию, метаболическую перепрограммирование и пространственные неоднородные ниши костного мозга, которые могут способствовать дисфункции Т-клеток и иммунной отток. В этом обзоре иммунологический синапс в качестве потенциально изменяемого межклеточного интерфейса: мы описываем, как ниша костного мозга влияет на синапти

Cell therapies in the clinic.

Cell therapies have emerged as a promising therapeutic modality with the potential to treat and even cure a diverse array of diseases. Cell therapies offer unique clinical and therapeutic advantages over conventional small molecules and the growing number of biologics. Particularly, living cells can simultaneously and dynamically perform complex biological functions in ways that conventional drugs cannot; cell therapies have expanded the spectrum of available therapeutic options to include key cellular functions and processes. As such, cell therapies are currently one of the most investigated

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… While most current CARs are only capable of recognizing cell surface antigens, TCRs recognize peptides derived from intracellular proteins by binding to major histocompatibility complex (MHC) class I molecules on target cells. …

Последствия Anti-CD20 Терапия антитела на Иммунной Клеточной Динамике в релапсирующих и излучающих Множестве склерозов.

ВВЕДЕНИЕ: Эффективность anti-CD20 :: борьба с антителами в значительной степени способствовала углублению понимания нами проблемы патогенеза заболеваний и улучшению результатов лечения при повторном выбросе множественных склерозов (РРМС). Был проведен всеобъемлющий анализ периферийных иммунных клеток в сочетании с перспективной клинической характеристикой пациентов RRMS, проходящих лечение острелизумаба (OCR) или атумумаба (OFA), в целях более глубокого понимания иммунной реконституции после истощения клеток B. МЕТОДЫ: REBELLION-MS представляет собой продольный анализ пациентов RRMS, проходящи

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… DN T cells, which lack CD4 and CD8 molecules necessary for stabilizing T-cell receptor-major histocompatibility complex (TCR-MHC) interactions, are involved in non-classical antigen presentation primarily through CD1 molecules [ 43 ]. …

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core sel

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… By means of click chemistry, the N 3 -tagged MNCs were conjugated with major histocompatibility complex class I and the co-stimulatory ligand anti-CD28. …

Immunologic and clinical effects of targeting PD-1 in lung cancer.

Therapeutic antibodies that block the programmed cell death protein-1 (PD-1) immune checkpoint pathway prevent T-cell downregulation and promote immune responses against cancer. Several PD-1 pathway inhibitors have shown robust activity in initial trials. This article reviews the preclinical evidence, rationale, and clinical pharmacology of blockade of PD-1 or its ligands as therapy for lung cancer and provides an overview of agents in development, clinical evidence to date, and implications for clinical application.

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… APC, antigen-presenting cell; IFN-γ, interferon-γ; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1, PD ligand 1; TCR, T-cell receptor. Reprinted from ref. 39 . …

Bacterial Bloodstream Infections after Allogeneic Hematopoietic Stem Cell Transplantation: Etiology, Risk Factors and Outcome in a Single-Center Study.

Background-Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are subject to major risks for bacterial bloodstream infections (BSIs), including emergent multidrug-resistant (MDR) organisms, which still represent the main cause of morbidity and mortality in transplanted patients.MethodsWe performed an observational, retrospective, single-center study on patients undergoing allo-HSCT between 2004 and 2020 at the Stem Cell Transplant Unit in Turin to assess the incidence, etiology, and outcomes of BSIs and to explore any risk factors for bacteriaemia.ResultsWe observed a total o

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… Durable engraftment of major histocompatibility complex–incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide Blood 2001 98 3456 3464 10.1182/blood.V98.12.3456 11719388 17. Carreras E. Dufour C. Mohty M. …

Clinical Characteristics, Comorbidities, and Treatment in Patients with Pemphigus-A Single-Center Retrospective Study.

BACKGROUND/OBJECTIVES: Pemphigus comprises a diverse group of disorders within the autoimmune bullous dermatoses (AIBDs) spectrum. Among these, pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are the most commonly encountered variants. Despite its rarity, this condition can pose a life-threatening risk. We aimed to assess clinical characteristics, comorbidities, medication, as well as the treatment of various types of pemphigus in pemphigus patients. METHODS: We gathered data from 69 patients treated in the Department of Dermatology in the years 2016-2023. The investigation included sex,

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… Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris Proc. Natl. Acad. Sci. USA 1991 88 5056 5060 10.1073/pnas.88.11.5056 1675792 PMC51806 52. Lombardi M.L. Mercuro O. Ruocco V. Lo Schiavo A. Lombari V. Guerrera V. Pirozzi G. Manzo C. …

From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies.

Background and objectiveTumor therapy is still a tough clinical challenge, and cancer immunotherapy has drawn increasing attention. T cells and natural killer (NK) cells play crucial roles in the immune response. Induced pluripotent stem cell (iPSC) technology opens up a new way to produce functionally improved universal iPSC-derived chimeric antigen receptor (CAR) T (CAR-iT) and iPSC-derived CAR-NK (CAR-iNK) cells. This study aims to comprehensively review the generation and clinical applications of iPSC-derived universal CAR-iT and CAR-iNK cells to explore their potential and future directio

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… The inhibitory receptors on NK cells include the killer cell immunoglobulin-like receptors (KIR) family and the CD94/NKG2A receptor, which recognize major histocompatibility complex (MHC)-I-like molecules on normal cells and subsequently prevent attacking on these cells by modulating NK cell activity …