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Understanding and Managing Sepsis in Patients With Cancer in the Era of Antimicrobial Resistance.

Sepsis is a frequent complication in immunosuppressed cancer patients and hematopoietic stem cell transplant recipients that is associated with high morbidity and mortality rates. The worldwide emergence of antimicrobial resistance is of special concern in this population because any delay in starting adequate empirical antibiotic therapy can lead to poor outcomes. In this review, we aim to address: (1) the mechanisms involved in the development of sepsis and septic shock in these patients; (2) the risk factors associated with a worse prognosis; (3) the impact of adequate initial empirical ant

CAR-Engineered Cell Therapies Beyond Cancer: Reprogramming Fibrosis and Immune-Mediated Inflammation.

Chimeric antigen receptor (CAR)-engineered cell therapies are being extended from hematological malignancies to autoimmune, inflammatory, and fibrotic diseases, although the maturity of evidence differs markedly among platforms and indications. Early clinical evidence from case reports, small case series, and early-phase trials suggests that CD19- or BCMA-directed CAR-T cells can induce deep B-cell or plasma-cell depletion and sustained remission in selected patients with refractory autoimmune diseases; however, their comparative efficacy, durability, and long-term safety remain incompletely d

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… Introduction Chimeric antigen receptor (CAR)‐engineered cell therapy has reshaped the treatment landscape of hematological malignancies by enabling major histocompatibility complex‐independent antigen recognition and potent effector‐cell activation. …

Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy.

Gamma delta (γδ) T cells are a minor population of T cells that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) T cells, γδ T cells are activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field of cancer immunotherapy progresses rapidly, different subsets of γδ T cells have been explored. In addition, γδ T cells can be engineered using different gene editing technologies that augment their tumor recognition abilities and antitumor functions. In this review, we

Recent advances in the management of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting highly heterogeneous clinical manifestations and multi-systemic involvement. Patients are susceptible to relapse- and remission, thus making management challenging. Moreover, a considerable number of side effects may occur with conventional therapies; therefore, there is clearly a need for new therapeutic strategies. Since the pathogenesis of SLE is highly complex, it is far from being fully understood. However, greater understanding of the pathways and of the cellular and molecular mediators involved in SLE is being

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… The mechanism of action of rigerimod is not fully understood, but preliminary studies showed that it acts as an immunomodulator by binding major histocompatibility complex (MHC) class II and consequently inhibiting T-cell reactivity and restoring immune tolerance 79 . …

Overhauling CAR T Cells to Improve Efficacy, Safety and Cost.

Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990's, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen recepto

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… Since CAR-based antigen recognition is mediated, typically, by a single chain antibody, there is no need for the antigen to be presented as a peptide by the major histocompatibility complex (MHC). …

Plasma Cell Myeloma: Биохимический анализ диагноза, лечения и умного нанокарьера - терапевтического развития.

Плазменная миелома (ПХМ) классифицируется как рак крови и характеризуется аномальным распространением плазменных клеток в костном мозге и чрезмерным производством моноколональных иммуноглобулинов, что приводит к постоянному повреждению жизненно важных органов. Несмотря на то, что стратегии лечения улучшились благодаря разработке протеазонных ингибиторов (ИП), иммуноводных препаратов (ИМИД) и моноклонных антител (mAbs), ПХМ остается неизлечимым заболеванием из-за молекулярной неоднородности и развития сопротивляемости лекарствам. В этом обзоре мы обсуждаем биохимические и молекулярные основы, л

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… Another important biomarker is β2-microglobulin (β2M), a protein associated with the class I major histocompatibility complex (MHC-I), found on the membrane of nearly all nucleated cells in the body, except red blood cells. …

An expanding horizon of complex injectable products: development and regulatory considerations.

There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" produ

Hematological Malignancy-Derived Small Extracellular Vesicles and Tumor Microenvironment: The Art of Turning Foes into Friends.

Small extracellular vesicles (small EVs) are commonly released by all cells, and are found in all body fluids. They are implicated in cell to cell short- and long-distance communication through the transfer of genetic material and proteins, as well as interactions between target cell membrane receptors and ligands anchored on small EV membrane. Beyond their canonical functions in healthy tissues, small EVs are strategically used by tumors to communicate with the cellular microenvironment and to establish a proper niche which would ultimately allow cancer cell proliferation, escape from the imm

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… Furthermore, TEV-carried ligands are recognized by proper receptors on target cells; for example, antigens carried by TEVs can bind to major histocompatibility complex (MHC) receptors [ 82 ]. …

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science.

Traditional Chinese medicine (TCM) has been practiced for thousands of years and at the present time is widely accepted as an alternative treatment for cancer. In this review, we sought to summarize the molecular and cellular mechanisms underlying the chemopreventive and therapeutic activity of TCM, especially that of the Chinese herbal medicine-derived phytochemicals curcumin, resveratrol, and berberine. Numerous genes have been reported to be involved when using TCM treatments and so we have selectively highlighted the role of a number of oncogene and tumor suppressor genes in TCM therapy. I

What Is Precision Psychotherapy?

Precision medicine impacts virtually all medical specializations, including psychiatry. Although precision psychiatry, in general, is a flourishing area of research and debate, psychotherapy as one pillar of psychiatry receives little attention. Theoretical discussions about precision psychotherapy are rare; research on precision in psychotherapy is just evolving. In this paper, we provide a conceptualization of precision psychotherapy providing a common idea of what should be understood as precision in the context of psychotherapy and what kind of psychotherapy research is considered to contr

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… This allergic reaction, however, could be correlated with a single genetic variant of the major histocompatibility complex class I (HLA-B*5701) ( Hetherington et al., 2002 ; Mallal, 2002 ). …

Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the

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… Recent research, using modern techniques previously mentioned, led to the implication of multiple genetic loci, with polymorphisms of Major Histocompatibility Complex (MHC) antigens having the primary role. 5.1. HLA 5.1.1. …

The Endocannabinoid System as a Pharmacological Target for New Cancer Therapies.

Despite the long history of cannabinoid use for medicinal and ritual purposes, an endogenous system of cannabinoid-controlled receptors, as well as their ligands and the enzymes that synthesise and degrade them, was only discovered in the 1990s. Since then, the endocannabinoid system has attracted widespread scientific interest regarding new pharmacological targets in cancer treatment among other reasons. Meanwhile, extensive preclinical studies have shown that cannabinoids have an inhibitory effect on tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and ep

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… Specifically, URB597 via induction of TIMP-3 expression was found to inhibit proteolytic shedding of the proteins major histocompatibility complex class I polypeptide-related sequence A (MICA) and B (MICB) on the surface of cancer cells, thereby ensuring binding of these proteins to the natural killer …

Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The type 1 diabetes patient cohort is highly heterogeneous, with individuals presenting with disease at different stages and severities, arising from distinct etiologies, and overlaying varied genetic backgrounds. At present, the "one-size-fits-all" treatment for type 1 diabetes is exogenic insulin substitution therapy, but this approach fails to achieve optimal blood glucose control in many individuals. Wit

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… Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor α chain gene rearrangement. Proc Natl Acad Sci. 1998;95(21):12538–12543. doi: 10.1073/pnas.95.21.12538. 122. …

Updates in novel immunotherapeutic strategies for relapsed/refractory AML.

Acute myeloid leukemia (AML) is a severe hematological malignancy with poor outcomes, particularly in older adults. Traditional treatment options like high-dose chemotherapy often lead to refractory or relapsed AML, with even worse outcomes. New therapies for relapsed and refractory AML are needed, and this review explores the most recent advancements in immunotherapy in AML. Checkpoint Inhibitors utilizing innate or adaptive immune targeting have shown potential to improve AML outcomes when combined with hypomethylating agents and chemotherapy. The use of adoptive cell therapy in AML demonstr

Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances.

Introduction: Acute lymphoblastic leukemia (ALL) is the first neoplasm where the assessment of early response to therapy by minimal residual disease (MRD) monitoring has proven to be a fundamental tool to guide therapeutic choices. The most standardized methods to study MRD in ALL are multi-parametric flow cytometry (MFC) and polymerase chain reaction (PCR) amplification-based methods. Emerging technologies hold the promise to improve MRD detection in ALL patients. Moreover, novel therapies, such as monoclonal antibodies, bispecific T-cell engagers, and chimeric antigen receptor T cells (CART)

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… Blinatumomab can bridge malignant B cells directly to CD3-positive T cells, bypassing TCR specificity and major histocompatibility complex (MHC) class I molecules ( 132 , 133 ) and induces T-cell activation, release of inflammatory cytokine production, specifically IL-2, IFN-γ, TNF-α, IL-4, IL-6, and …

Measurable Residual Disease Testing During Treatment with Bispecific Antibodies for Lymphoma.

The introduction of bispecific antibodies (BsAbs) has led to significant improvements in survival for patients with relapsed and refractory B-cell lymphomas. Despite these advances, there remains a significant number of patients who experience disease progression after these novel therapies. Predicting which patients may respond to certain treatments and the durability of their responses remains challenging. Measurable residual disease (MRD) has become easier to detect and quantify through the use of genomic next-generation sequencing tools and has been studied as a possible biomarker to predi

Площадь метилирования ДНК клеток цереброспинальной жидкости в множестве склероза: исследование эпигеномной ассоциации.

Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, в которой метилация ДНК может увязывать генетические и экологические факторы риска. Methods: Мы профилировали содержание метилации ДНК по всему геному в клетках цереброспиновой жидкости (CSF) у людей с MS (pwMS) и совпадающими контрольными устройствами. Дифференцированные метилированные позиции (DMP) и регионы (DMR) были интегрированы с транскриптомными данными, аннотациями клеточного хроматина Т и анализом путей. Выражение гамма-протокадерина (ПХДГ) было оценено в первичных подмножествах C

GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of t

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… GD2-based CAR-T cell therapy One of the most significant advancements in the onco-immunotherapy field involves the development of T cells engineered with CAR to target a specific antigen expressed at the surface of the tumor cells in a major histocompatibility complex (MHC)-independent manner. …

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-

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… When IL-1β was involved, FGF-2 stimulation led to increased levels of the membrane-bound major histocompatibility complex class I-related chain A (MICA)—which is an NK cell activation molecule—as well as decreased levels of human leukocyte antigen (HLA) class I—which is an NK cell inhibitor. …

Beyond DNA Damage: Exploring the Immunomodulatory Effects of Cyclophosphamide in Multiple Myeloma.

The alkylating agent cyclophosphamide has been used in the treatment of multiple myeloma for over 60 years. At low doses, cyclophosphamide also has significant immunomodulatory activity, which can be used to modify the immunosuppressive tumor microenvironment in order to augment responses to existing therapies. Immune-mediated therapies are becoming more widespread in modern approaches to myeloma treatment. In this review, we discuss the effects cyclophosphamide has on the immune system, and how it can be used synergistically with other treatment modalities including the immunomodulatory agent

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… Effector T cells CD8 expressing T cells recognize antigen displayed by MHC Class I (major histocompatibility complex) present on the majority of nucleated cells. Once activated they release the contents of their cytotoxic granules leading to cellular apoptosis. …