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Current Status of Gene Engineering Cell Therapeutics.

Ex vivo manipulations of autologous patient's cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to in

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… In addition, one of the main advantages of autologous therapies is their full major histocompatibility complex (MHC) compatibility leading to a better engraftment and persistence of the cells and a low risk of graft versus host disease (GvHD). …

Nanomedicine Meets Immunotherapy: Advancing Adoptive Cell Therapy with Nanoparticles in the Treatment of Cancer with Sustainability Perspectives.

Immunotherapy has achieved remarkable clinical success in certain cancers, particularly through adoptive cell therapy (ACT), where T cell engineering with chimeric antigen receptor (CAR) has driven major clinical breakthroughs in the treatment of hematologic malignancies. However, efficacy against solid tumors remains limited due to multiple barriers, including the scarcity of tumor-specific antigens, antigen heterogeneity, immunosuppressive tumor microenvironment, and physical obstruction of T cell infiltration by dense extracellular matrix. Nanoparticle (NP)-based approaches can overcome the

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… Unlike CAR T cells, which target surface antigens, TCR T cells are designed to recognize intracellular antigens presented via the major histocompatibility complex (MHC). This allows TCR T cells to access a broader repertoire of tumor‐associated antigens. …

Иммуномодулирующий и противовоспалительный потенциал S-нитросглутатиона (GSNO) при множественной склерозе: обзор механизмов и терапевтических перспектив.

Многофакторная демиелинизация (МС) — это хроническое аутоиммунное заболевание центральной нервной системы (СНС), характеризующееся длительной нейроинфляминацией, окислительным стрессом, демиелинизацией и прогрессирующей нейродегенерацией. Несмотря на то, что МС остается неизлечимым, современные терапевтические средства (ТМС) помогают снизить частоту обострений и задерживать прогрессирование заболевания. Недавно разработанные инъекционные и инфузийные биологические ТМС обеспечивают целенаправленную иммуномодуляцию, но их клиническая полезность ограничена родственными методами введения и возможн

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… Among the genetic risk factors, variations within the major histocompatibility complex (MHC) region, especially in human leukocyte antigen (HLA) genes, which play a key role in helping T cells recognize foreign antigens, have been strongly associated with increased susceptibility to MS ( 2 , 3 ). …

Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).

Cancer therapy has undergone a remarkable evolution over the past few decades, driven largely by innovations in medicinal chemistry. This review explores the pivotal role of medicinal chemistry in designing, optimizing, and classifying anticancer agents, from traditional cytotoxics to modern targeted therapies, immunotherapies, and radiotheranostics. The article categorizes FDA-approved anticancer drugs (2015-2025), evaluates their mechanisms of action, structural features, and structure-activity relationships (SAR), and highlights both success stories and challenges in clinical translation. A

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… Its SAR focuses on optimized antigen selection for immunogenicity, epitope refinement to boost major histocompatibility complex class I (MHC-I) binding and CD8 + T-cell responses, and a plasmid backbone engineered for efficient expression and safety. …

Emerging new therapeutic antibody derivatives for cancer treatment.

Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells. The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies, such as antibody fragments, bispecific antibodies, and antibody derivatives (e.g., antibody-drug conjugates and immunocytokines). The miniaturization and multifunctionalization of antibodies are flexible and viable strategies for diagnosing or treating malignant tumors in a complex t

Emerging Therapies in the Management of Advanced-Stage Gastric Cancer.

Globally, gastric malignancy contributes to significant cancer-related morbidity and mortality. Despite a recent approval of two targeted agents, trastuzumab and ramucirumab, the treatment options for advanced-stage gastric cancer are limited. Consequently, the overall clinical outcomes for patients with advanced-stage gastric cancer remain poor. Numerous agents that are active against novel targets have been evaluated in the course of randomized trials; however, most have produced disappointing results because of the molecular heterogeneity of gastric cancer. The Cancer Genome Atlas (TCGA) pr

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… It competes with CD4 to bind the major histocompatibility complex (MHC) II. The binding of LAG-3 to MHC II molecules results in the down-regulation of CD4 + antigen-specific T-cell proliferation and cytokine secretion. LAG-3 is expressed on both Tregs and anergic T-cells (He et al., 2016 ). …

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.

Cancers are highly complex diseases that are characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming of the immune system play critical roles in tumor initiation and progression. Immunotherapy aims to reactivate antitumor immune cells and overcome the immune escape mechanisms of tumors. Represented by immune checkpoint blockade and adoptive cell transfer, tumor immunotherapy has seen tremendous success in the clinic, with the capability to induce long-term regression of some tumors that are refractory to all other treatm

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… The first signal is an antigen-specific signal, which involves the specific binding of the T-cell surface receptor (TCR) to the antigenic peptide-major histocompatibility complex (MHC). 11 , 12 The second signal is mediated by the communication of T cells with costimulatory molecules (CMs) on the surface …

Abstracts from the 8th Drug Hypersensitivity Meeting (DHM)

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Advancing CAR T-Cell Therapy in Solid Tumors: Current Landscape and Future Directions.

BackgroundChimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment of hematological malignancies, yet its application in solid tumors remains constrained by unique biological and logistical barriers.ObjectiveThis review critically examines the evolving landscape of CAR T-cell therapy in solid malignancies, with a focus on antigen heterogeneity, the immunosuppressive tumor microenvironment, and risks of on-target, off-tumor toxicity.MethodsWe outline recent advances in CAR engineering, including co-stimulatory optimization, dual- and multi-antigen targeting, armored CARs, an

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… These CARs combine the antigen-binding domains of monoclonal antibodies with intracellular T-cell signaling domains to induce T-cell activation independently of Major Histocompatibility Complex (MHC) recognition. …

The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis.

Although it has long been recognized that inflammation, a consequence of immune-driven processes, significantly impacts bone turnover, the degree of centralization of skeletal and immune functions has begun to be dissected only recently. It is now recognized that formation of osteoclasts, the bone resorbing cells of the body, is centered on the key osteoclastogenic cytokine, receptor activator of NF- κ B ligand (RANKL). Although numerous inflammatory cytokines are now recognized to promote osteoclast formation and skeletal degradation, with just a few exceptions, RANKL is now considered to be

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… CD4 + T cell activation requires two distinct signals, the first signal of which is generated by engagement of the T-cell receptor (TCR) on CD4 + helper T cells with major histocompatibility complex (MHC) class II (MHCII) bearing antigens on the surface of professional antigen presenting cells (APCs) …

Cancer-Therapy-Related Cardiac Dysfunction: Latest Advances in Prevention and Treatment.

The increasing efficacy of cancer therapies has significantly improved survival rates, but it has also highlighted the prevalence of cancer-therapy-related cardiac dysfunction (CTRCD). This review provides a comprehensive overview of the identification, monitoring, and management of CTRCD, a condition resulting from several treatments, such as anthracyclines, HER2-targeted therapies, target therapies, and radiotherapy. The paper includes a discussion of the mechanisms of CTRCD associated with various cancer treatments. Early detection through serum biomarkers and advanced imaging techniques is

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… Moreover, statins have immunomodulatory effects, such as reducing the expression of major histocompatibility complex class II, which dampens the immune response by decreasing T cell proliferation and regulating T cell differentiation. …

Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.

Gastrointestinal malignant tumors exhibit a high incidence and mortality rate among all malignancies worldwide, making them a significant concern within the field of oncology. Targeted therapy for gastrointestinal tumors has become a hot topic in recent years, and its specific mechanism remains to be further elucidated. Secreted factors, including cytokines, chemokines, and growth factors, as components of the tumor microenvironment, play a crucial role in the progression of gastrointestinal tumors. Interferon-gamma (IFN-γ) can activate these factors through JAK1/2 and STAT1 signaling (the IFN

Deciphering and targeting oncogenic pathways through integrated approaches and amino acid metabolism in hematologic malignancies.

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, represent a diverse group of blood cancers driven by complex oncogenic pathways and genetic aberrations. Despite advances in treatment, resistance and relapse remain significant clinical challenges. This review presents an integrative approach to blood cancer therapy, highlighting the convergence of precision medicine, CRISPR-based gene editing, immunotherapy (including CAR-T cells and immune checkpoint inhibitors), and targeted modulation of amino acid metabolism. We investigate the molecular pathways driving tumour

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy.

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening co

Revolutionizing the treatment for nasopharyngeal cancer: the impact, challenges and strategies of stem cell and genetically engineered cell therapies.

Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the nasopharynx and is consistently associated with the Epstein-Barr virus (EBV) infection. Its unique anatomical location and complex aetiology often result in advanced-stage disease at first diagnosis. While radiotherapy (RT) and chemotherapy have been the mainstays of treatment, they often fail to prevent tumour recurrence and metastasis, leading to high rates of treatment failure and mortality. Recent advancement in cell-based therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown great promise in hematologic

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… CAR, Chimeric antigen receptor; LMP, Latent membrane protein; EBV, Epstein-Barr virus; IL-2, Interleukin-2; IFN-γ, Interferon-γ; TCR, T cell receptor; MHC, Major histocompatibility complex; HLA, Human leukocyte antigen; NK, Natural killer; F3, Coagulation factor III; PD-1, Programmed cell death receptor …

Immunomodulatory Nanosystems.

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off-target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provi

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… Nanoparticles for T Cell Activation : The presentation of tumor antigens with the participation of major histocompatibility complex I (MHCI) molecules is pivotal for the activation of CD8+ T cell response, which is mainly responsible for recognition of endogenous cytosolic antigens and elimination of …

Abstracts of the Cell Therapy Transplant Canada 2022 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2022 Annual Conference. The conference was held in-person 15-18 June 2022, in Niagara Falls, Ontario. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 16 June, and oral abstract authors were featured during the oral abstract session in the afternoon on Friday, 17 June 2022. Thirty-three (33) abstracts were selected for presentation as posters and six (6) as oral presentations. The top abstracts in each of four (4) categories, (1) Basic/Translati

Next-generation antibody-based therapeutics in cancer: antibody-drug conjugates bispecific antibodies across hematologic malignancies and solid tumors.

The therapeutic paradigm in oncology is undergoing a profound transformation driven by antibody-drug conjugates (ADCs) and bispecific antibodies (bsAbs). This review comprehensively summarizes recent clinical advances of these platforms across both hematologic malignancies and solid tumors. ADCs such as trastuzumab deruxtecan have expanded the concept of targetable HER2 expression, demonstrating meaningful intracranial activity and redefining standards of care in HER2-low breast cancer and beyond. The landscape continues to broaden with novel ADC targets (TROP2, CLDN18.2, B7-H3, HER3) and bisp

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… Its mechanism of action—simultaneously binding CD3 on T cells and CD19 on B-lineage cells to form a cytolytic synapse—enables potent, polyclonal T-cell-mediated killing independent of major histocompatibility complex restriction or costimulation [ 134 ]. …

Иммунотерапия Множественной миеломы: Текущий статус как пролог в будущее.

Площадь терапевтических мер по лечению множественной миеломы претерпела сейсмические изменения с начала нынешнего столетия. Это было обусловлено главным образом введением новых классов небольших молекул, таких, как протеазонные блокаторы (например, бортезомиб) и иммуноводители (например, линалидомид), а также иммунотерапевтическими агентами, начиная с anti-CD38 Моноклональная антитела Daratumumab 2015. В последнее время в арсенал лекарств, доступных для борьбы с этим злоумышленником, добавились и другие иммунотерапии. В их число входят продукты биконкретных теклистамб, талькетамаб и эльранатам

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… Bispecific antibodies provide certain theoretical benefits by circumventing certain processes normally associated with immune responses, such as costimulatory molecules, antigen-presenting cells, or the interplay between antigens and major histocompatibility complexes (MHC). …

The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in

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… One intriguing difference between melanoma and epithelial cancers was that a higher percent of T cell responses to neoantigens were mediated by CD4+cells and were likely major histocompatibility complex (MHC) Class II restricted in epithelial cancers (54% vs approximately 25% for melanoma). …