Результаты поиска

T-cell Immunotherapies and the Role of Nonclinical Assessment: The Balance between Efficacy and Pathology.

Gene-engineered T-cell therapies have the potential to revolutionize the treatment of cancer. These therapies have shown exceptional clinical efficacy specifically in the field of B-cell malignancies and the first products (Kymriah™ and Yescarta™) have recently been approved in the United States for specific indications. The power of these treatments is also linked with a distinct set of toxicities both predicted and unpredicted, including off-tumor activity, cytokine release syndromes, and neurotoxicity, occasionally with fatal consequences. As these therapies begin to reach more patients, it

Совпадение в полном тексте источника
… The TCR confers antigenic specificity on the T cell, by recognizing an antigen ligand comprising a short contiguous amino acid sequence of a protein that is presented on the target cell by a major histocompatibility complex (MHC) molecule. … The TCR confers antigenic specificity on the T cell by recognizing an antigen ligand comprising a short contiguous amino acid sequence of a protein that is presented on the target cell by a major histocompatibility complex (MHC) molecule ( Figure 1A ). …

Harnessing Immune Response in Acute Myeloid Leukemia.

Despite the results achieved with the evolution of conventional chemotherapy and the inclusion of targeted therapies in the treatment of acute myeloid leukemia (AML), survival is still not satisfying, in particular in the setting of relapsed/refractory (R/R) disease or elderly/unfit patients. Among the most innovative therapeutic options, cellular therapy has shown great results in different hematological malignancies such as acute lymphoblastic leukemia and lymphomas, with several products already approved for clinical use. However, despite the great interest in also expanding the application

Совпадение в полном тексте источника
… Indeed, the downregulation of Major Histocompatibility Complex type 1 (MHC-1) and costimulatory molecules on tumor cells represent the main immunological escape mechanism towards T cells. …

Oncolytic myxoma virus and engineering strategies for advanced cancer immunotherapy.

In cancer immunotherapy, oncolytic viruses (OVs) offer an alternative approach to kill malignant cells by inducing cancer-specific host immune system activation. Given the ongoing need for safe and effective viral vectors for immunotherapy, non-zoonotic animal viruses have attracted significant interest. Here, we review the oncolytic myxoma virus (MYXV) and emphasize its emerging role in cancer immunotherapy. We critically discuss recent advances in cancer therapy using MYXV, primarily focused on engineered viral modifications. Furthermore, we briefly review alternative delivery strategies for

Совпадение в полном тексте источника
… These antigens are then captured by antigen-presenting cells (APCs), such as dendritic cells (12), and presented in the tumor-infiltrating lymph nodes as part of major histocompatibility complex (MHC) class I/II molecules to CD8 + and CD4 + T cells, respectively (13). … histocompatibility complex (MHC) expression facilitate immune evasion in cancer and allow the disease to spread. 80 Monotherapies are often insufficient as they can lead to drug resistance due to the heterogeneity and complex genetic mutation burden in tumors and complex TME. …

Current advancements in cellular immunotherapy for autoimmune disease.

The management of autoimmune diseases is currently limited by therapies that largely suppress the immune system, often resulting in partial and temporary remissions. Cellular immunotherapies offer a targeted approach by redirecting immune cells to correct the underlying autoimmunity. This review explores the latest advances in cellular immunotherapies for autoimmune diseases, focusing on various strategies, such as the use of chimeric antigen receptor (CAR) T cells, chimeric auto-antibody receptor (CAAR) T cells, regulatory T cells (Tregs), and tolerogenic dendritic cells (TolDCs). We review r

Совпадение в полном тексте источника
… Peptide: Major Histocompatibility complex 2 (p: MHCII) CAR T cells specifically target autoreactive CD4 T cells by incorporating the beta chain of an MHCII ab dimer. … Peptide: Major histocompatibility complex 2 (p: MHCII) CAR T Recent developments have introduced a new level of precision in targeting CD4 + T cells, critical mediators of autoimmune disease [ 30 ]. …

Roles of LINC01473 and CD74 in osteoblasts in multiple myeloma bone disease.

The suppression of osteoblast (OB) activity is partially responsible for multiple myeloma (MM) bone disease. Long non-coding RNAs (lncRNAs) play a vital role in bone formation and resorption. However, their functions in OBs from patients with MM have rarely been reported. Through high-throughput sequencing of OBs from patients with MM and healthy controls, we identified several lncRNAs and messenger RNAs (mRNAs) with different expression profile and validated them using quantitative real-time PCR. In total, 22 upregulated and 21 downregulated lncRNAs were found in OBs from patients with MM. Mo

Совпадение в полном тексте источника
… CD74 (major histocompatibility complex (MHC) II associated unchanging chain) is a type II transmembrane glycoprotein that plays a critical role in antigen presentation as a chaperone of MHC class II proteins. 27 CD74 can be detected in traditional antigen-presenting cells (APCs; B cells, dendritic cells …

Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common and aggressive cancer with a high mortality rate. The incidence of HCC is increasing worldwide, and the lack of effective screening programs often results in delayed diagnosis, making it a challenging disease to manage. Immunotherapy has emerged as a promising treatment option for different kinds of cancers, with the potential to stimulate the immune system to target cancer cells. However, the current immunotherapeutic approaches for HCC have shown limited efficacy. Since HCC arises within a complex tumour microenvironment (TME) characterized by the p

Совпадение в полном тексте источника
… Two different kinds of tumour-associated antigens (TAA) are recognized: non-mutated self-antigens, which are Major Histocompatibility Complex I (MHC-I) restricted antigens, and Major Histocompatibility Complex II (MHC-II) restricted antigens, which arise from non-synonymous somatic mutations [ 35 ]. …

Парадокс ХЛА среди различных групп населения в процессе склероза: систематический обзор.

Множественный склероз (МС) свидетельствует о неоднородности курсов по болезням. Несмотря на то, что ХЛА ДРБ1*15::01 представляет собой самый сильный фактор генетического риска для MS-чувствительности, принося примерно в три раза больший риск, не влияет ли эта аллея на прогрессию заболеваний по-прежнему спорным образом. МЕТОДЫ: Этот систематический обзор был проведен с целью уточнения взаимосвязи между полиморфизмом ВЛА и ходом многочисленных склерозов с момента их создания до ноября 2025. A three- для учета ненезависимости статистических данных использовался метаанализ случайного воздействия н

Совпадение в полном тексте источника
… It combined controlled vocabulary and free-text terms as follows: (("HLA"[Title/Abstract] OR "human leukocyte antigen"[Title/Abstract] OR "major histocompatibility complex"[Title/Abstract] OR "MHC"[Title/Abstract]) AND ("progress*"[Title/Abstract] OR "disability"[Title/Abstract] OR "severity"[Title/Abstract …

The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis.

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metast

Совпадение в полном тексте источника
… Radiotherapy is also known to upregulate major histocompatibility complex class I (MHC-I) expression [ 99 , 100 ], which is commonly downregulated in cancerous tissue [ 101 ] and associated with poor survival [ 102 , 103 ]. … Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer Br. J. Cancer 2015 113 1343 1349 10.1038/bjc.2015.337 26461054 PMC4815783 104. Reits E.A. Hodge J.W. Herberts C.A. Groothuis T.A. Chakraborty M. Wansley E.K. …

Роли глюкагонового пептида 1 Агонисты-рецепторы в биологии иммунных клеток и аутоиммунных/аутоинфлампмидативных заболеваниях.

Глукагон-подобный peptide-1 (В тыс.GLP-1) — гормон, полученный кишечником, необходимый для поддержания глюкозы гомеостаза через многочисленные физиологические пути: инсулина, ингибирующего секрецию глюкагонов, замедляющего опустошение желудочков, усиливающего чувство полноты и подавляющего аппетит. С тех пор GLP-1 может разлагаться при помощи дипептидила пептидаза 4, GLP-1 рецепторные агонисты (GLP-1RAs) были разработаны для решения этой проблемы деградации. В настоящее время GLP-1RAs стали высокоэффективными методами лечения для управления типом 2 сахарный диабет и ожирение. Помимо их хорошо

Совпадение в полном тексте источника
… As opposed to αβ T cells, γδ T cells are not limited by major histocompatibility complex (MHC) molecules [ 152 ]. … These molecules share structural similarities with major histocompatibility complex class I (MHC-I) proteins [ 159 ]. …

Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.

The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the po

Совпадение в полном тексте источника
… Another important receptor, NKG2A, interacts with the major histocompatibility complex (MHC) class I molecule human leukocyte antigen E (HLA-E) to suppress NK cytotoxicity and maintain immune homeostasis [ 105 , 106 ]. … In addition, variable fragments of T cell receptor (TCR)-like antibodies in CAR-T cells recognize intracellular antigen-derived peptide/major histocompatibility complex (pMHC). This enables CAR-T cells to overcome cell surface barriers [ 142 ], presenting promising prospects for related therapies. …

Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease.

Graft versus host disease (GVHD) is the major non-relapse complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, GVHD occurs in roughly half of patients following this therapy and can induce severe life-threatening side effects and premature mortality. The pathophysiology of GVHD is driven by alloreactive donor T cells that induce a proinflammatory environment to cause pathological damage in the skin, gastrointestinal (GI) tract, lung, and liver during the acute phase of this disease. Recent work has demonstrated that the GI tract is a pivotal ta

Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.

Natural killer (NK) cells are a crucial part of the innate immune system and serve as an important effector for killing tumor cells through direct cytolytic activity or immunomodulatory signaling to T cells and antigen presenting cells. NK cells are correlated with increased tumor control and better overall patient survival across various types of cancers including non-small cell lung cancer (NSCLC). Despite their promising potential for anti-tumor killing, NK cell function is often diminished within the tumor microenvironment. There are many factors that lead to decreased tumor-infiltrating N

Tabelecleucel in Post-transplant Epstein-Barr Virus-Associated Lymphoproliferative Disease: Patient and Oncologist Perspectives.

This article is coauthored by the parents of a young patient and the medical team who cared for her.Together, they recount their shared experience with tabelecleucel, a novel therapy for Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV + PTLD). The patient's parents offer a deeply personal perspective, reflecting on several years of struggle marked by unwavering hope and trust in the medical professionals who have supported their daughter throughout her journey. The pediatric hemato-oncologist who advocated for the use of tabelecleucel described the case as unique

Совпадение в полном тексте источника
… Three years later, at the time of this writing, she remains off immunosuppressive therapy. ‘ This young girl underwent a multi-visceral transplant (including pancreas, stomach, gut, and liver) from a fully major histocompatibility complex-mismatch deceased donor.’ …

Нейтрофилы, НЕТ и множественный склероз: мини-обзор.

Множественный склероз (MS), хроническое аутоиммунное и дегенеративное заболевание, характеризующееся активацией различных провокационных клеток, приводит к обезвоживанию и нейрональным травмам. Нейтрофилы, которые часто недооцениваются в MS, получают все большее внимание за свои важные функции у пациентов MS и экспериментальную аутоиммунную энцефаломиелитную модель (EAE). Нейтрофилы играют многообразную роль в посредничестве патогенеза аутоиммунных заболеваний, и многочисленные исследования свидетельствуют о том, что нейтрофилы могут играть решающую роль благодаря образованию нейтрофильной вне

Совпадение в полном тексте источника
… Within the adaptive immune system, T cells play a vital role in recognizing specific antigens presented by antigen-presenting cells (APCs) through major histocompatibility complex (MHC) molecules. …

Intestinal barrier functions in hematologic and oncologic diseases.

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complica

Oral complications and management strategies for patients undergoing cancer therapy.

With cancer survival rate climbing up over the past three decades, quality of life for cancer patients has become an issue of major concern. Oral health plays an important part in one's overall quality of life. However, oral health status can be severely hampered by side effects of cancer therapies including surgery, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. Moreover, prevention and treatment of these complications are often overlooked in clinical practice. The present paper aims at drawing health care professionals' attention to oral complications associated wit

Translational strategy to support the first-in-human study of a TCR-like T cell bispecific with an in vitro-based safety approach.

The nonclinical development of T-cell receptor (TCR)-based therapeutics is uniquely challenged by the human-exclusive specificity of the peptide-HLA target, rendering conventional animal models unsuitable for safety assessment. To support first-in-human (FIH) studies in patients with solid tumors with the novel TCR-like T Cell Bispecific (TCB) antibody MAGE-A4-TCB, targeting the MAGE-A4 peptide presented by HLA-A*02:01 and engaging T-cells via the CD3ϵ chain, we implemented a comprehensive, prediction-independent safety strategy relying on New Approach Methodologies (NAMs). This approach utili

Совпадение в полном тексте источника
… Two human Fab domains bind to human MAGE-A4230-239 (GVYDGREHTV) peptide-major histocompatibility complex (pMHC) of the human leukocyte antigen (HLA)-A*02 allotype on MAGE-A4 positive tumor cells ( 21 ). One humanized Fab domain binds to the human CD3ϵ chain on T−cells ( Figure 1 ). … Simultaneous binding to tumor-expressed pMHC and T-cell CD3 mediates T-cell activation, degranulation, and subsequent tumor cell lysis. hCD3e, human CD3 ϵ chain; MAGE-A4, melanoma-associated antigen 4; pMHC, peptide-major histocompatibility complex; TCB, T-cell bispecific antibody; VH, variable domain …

Гетерогенность регулируемых клеток В в аутоиммунных заболеваниях: последствия для иммунного равновесия и терапевтических стратегий.

Регулирующие клетки В (Bregs) играют ключевую роль в поддержании иммунной терпимости и профилактике аутоиммунных заболеваний. Однако в условиях аутоиммунной среды количество и функции брега часто ухудшаются, что ведет к провоспалительной микроокружающей среде и регулированию иммунной дизакции. В рамках этого обзора проводится углубленный анализ последствий различных аутоиммунных заболеваний, включая множественный склероз, ревматоидный артрит, системный волчанье эритематосус, болезнь Шёгрена, аутоиммунный диабет и другие аутоиммунные заболевания. Резюмируя изменения в фенотипе Брегса и его функ

Совпадение в полном тексте источника
… Other molecules, including major histocompatibility complex class Ⅱ transactivator (CⅡTA), poly (ADP) ribose polymerase 1 (PARP-1), B-cell lymphoma 3 (Bcl-3), IFN-γ, and signaling lymphocytic activation molecule family member 5 (SLAMF5), have also been shown to suppress IL-10 expression [ 27 , 28 ]. …

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer.

Adoptive cell therapy (ACT) is an approach to cancer treatment that involves the use of antitumor immune cells to target residual disease in patients after completion of chemo/radiotherapy. ACT has several advantages compared with other approaches in cancer immunotherapy, including the ability to specifically expand effector cells in vitro before selection for adoptive transfer, as well as the opportunity for host manipulation in order to enhance the ability of transferred cells to recognize and kill established tumors. One of the main challenges to the success of ACT in cancer clinical trials

Совпадение в полном тексте источника
… Inhibitory receptors for major histocompatibility complex (MHC) class I molecules include killer immunoglobulin‐like receptors (KIRs), which bind human leukocyte antigen (HLA)‐A, B, and C, and the CD94‐NKG2A heterodimer, which recognizes HLA‐E. … Major histocompatibility complex class I‐related chain a and UL16‐binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D‐dependent natural killer cell cytotoxicity . …

miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy.

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system's multiple signalling pathways by binding to the

Совпадение в полном тексте источника
… APCs are immune cells that have a portentous component known as major histocompatibility complex I or II (MHC-I or II) on its surface [ 112 ]. APCs digest the antigens and display appropriate protein fragments bounded to the MHC, identified by the T-cells and activated. … Further, alterations in the major histocompatibility complex-1 and transporters of antigens processing mutation restrict the identification of cancer cells and, thus, promote cancer immune escape [ 124 ]. …