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Antibody Therapeutics as Interfering Agents in Flow Cytometry Crossmatch for Organ Transplantation.

Donor-recipient matching is a highly individualized and complex component of solid organ transplantation. Flowcytometry crossmatching (FC-XM) is an integral step in the matching process that is used to detect pre-formed deleterious anti-donor immunoglobulin. Despite high sensitivity in detecting cell-bound immunoglobulin, FC-XM is not able to determine the source or function of immunoglobulins detected. Monoclonal antibody therapeutic agents used in a clinic can interfere with the interpretation of FC-XM. We combined data from the prospectively maintained Antibody Society database and Human Pr

Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond onco

Dawn of CAR-T cell therapy in autoimmune diseases.

AbstractChimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy hold

Advances in the treatment of systemic lupus erythematosus: Biologicals, small-molecular agents, and cell-depleting therapies coming to the clinic.

Systemic lupus erythematosus (SLE; lupus) remains a particular challenge for the practicing clinician on account of its chronic undulating and unpredictable course, its diverse manifestations, and-until recently-limited treatment options all associated with considerable downsides. However, a major change in this situation is currently taking place. Over the past few years, several new biological therapeutics have been approved for the treatment of SLE (belimumab and anifrolumab) or specifically for its renal organ manifestation (obinutuzumab), along with one new small molecular treatment for t

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

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… Chimeric autoantigen T cell receptor (CATCR) T cells incorporate an autoantigen into a T cell receptor CD3 complex to target autoreactive B cells. CATCR targeting B cells expressing autoantibodies to beta-2-glycoprotein are currently under preclinical investigation. … The CATCR construct incorporates an autoantigen into a T cell receptor (TCR)-CD3 complex. The CATCR is then expressed in patient T cells, whose endogenous TCR is disrupted in parallel (Fig. 1 ). …

Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors.

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural

Эволюционный план лечения для пожилых пациентов с множественной миеломой: от квадских режимов до T-Cell Workers и CAR-T.

Множественная миелома (ММ) является главным образом болезнью пожилых людей. В последние годы резкое увеличение числа высокоэффективных методов лечения плазменных клеток привело к революции в уходе за престарелыми пациентами, страдающими миеломой (ММ), для которых слабые и связанные с возрастом конкурирующие причины смертности определяют управление. Традиционно лечение вновь диагностированных пожилых пациентов было сосредоточено на двойных или тройных комбинациях, состоящих из иммуномодуляторов (ИМИД), протеазонных ингибиторов (ИП), anti-CD38 моноклонные антитела (mAbs) и кортикостероиды, обесп

Perspectives on the Treatment of Multiple Myeloma.

The treatment of multiple myeloma has evolved significantly over the past few decades with the development of novel therapeutics. The introduction of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and high-dose chemotherapy followed by hematopoietic stem cell transplantation has led to improved response rates and survival outcomes. The use of bispecific antibodies and chimeric antigen receptor T-cell therapy is currently under study, and early results are showing promise. Although outcomes for patients with MM have improved with the development of new treatments, there r

Progress of immune senescence in multiple myeloma treatment resistance.

Multiple myeloma has become the second most common hematologic malignancy threatening human health with the increasing incidence in the population, and the emergence of drug resistance in its treatment has become a problem that needs to be solved urgently. Recent studies have shown that the immune system is closely related to the development of multiple myeloma, and immune senescence plays an extremely critical role in MM treatment resistance. In this paper, we review the connection between immune senescence and the development of MM and its possible role in the drug resistance of MM treatment

Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.

Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting. Genetically engineered T cells express chimeric antigen receptors (CARs), which can detect signals expressed by the molecules present on the surface of cancer cells, also called tumor-associated antigens (TAAs). Their effectiveness has been extensively demonstrated in hematological cancers; therefore, these results can establish th

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

Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recog

Иммунофенотифицирование крови пациентов с множественным склерозом в диагнозе указывает на классическую подгруппу моноцитов, связанную с эволюцией болезней.

ВВЕДЕНИЕ: Торговля миелоидными клетками с периферии в центральную нервную систему является ключевым фактором в многократном склерозе (МС) посредством представления антигенов, секреции цитокинов и процессов ремонта. МЕТОДЫ: Комбинация массовой цитометрии на кровяных клетках от 60 пациентов, проходящих диагностику, и 29 здоровых методов контроля, а также секвенирование с одной клеткой РНК на спаренных образцах крови и цереброспинной жидкости (CSF), взятых из 5 пациентов с миэлоидными клетками. Результаты: Исследование отсека Myeloid показало обогащение специфической классической популяции моноци

Integrative multi-omics analysis reveals CXCL10-driven inflammation and TREM2 + macrophage-plasma cell survival niche as hallmarks of late-stage rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by persistent synovial inflammation, yet the molecular mechanisms distinguishing early from late-stage disease remain incompletely elucidated. Identifying stage-specific biomarkers and pathogenic cellular interactions is crucial for precision medicine. OBJECTIVE: To comprehensively characterize the transcriptomic landscape and cellular composition of early versus late RA synovium, identify diagnostic biomarkers, and elucidate key pathogenic cell–cell interactions driving disease chronicity. METHODS: Synovial tissues from 51 RA patients (13

Сокращение ячеек не улучшает восстановления мышей при искусственном обезвоживании аутоиммунной энцефаломиэлитом (EAE).

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся демиэлированием на основе иммунных клеток и прогрессивным нейродегенерацией. В последнее время в хронических поражениях MS наблюдались чувствительные клетки (КЦ), что указывает на их возможное участие в прогрессии заболеваний. Вместе с тем роль СК и потенциальные терапевтические выгоды их сокращения с помощью сенолитной терапии еще предстоит определить в экспериментальной аутоиммунной энцефаломиелите (EAE), широко используемой доклинической модели MS. Здесь мы показываем, чт

Placental circulating T cells: a novel, allogeneic CAR-T cell platform with preserved T-cell stemness, more favorable cytokine profile, and durable efficacy compared to adult PBMC-derived CAR-T.

BACKGROUND: Chimeric antigen receptor (CAR)-T cell quality and stemness are associated with responsiveness, durability, and memory formation, which benefit clinical responses. Autologous T cell starting material across patients with cancer is variable and CAR-T expansion or potency can fail during manufacture. Thus, strategies to develop allogeneic CAR-T platforms including the identification and expansion of T cell subpopulations that correspond with CAR-T potency are an active area of investigation. Here, we compared CAR-T cells generated from healthy adult peripheral blood T cells versus pl

γδ T Cell Immunotherapy-A Review.

Cancer immunotherapy utilizing Vγ9Vδ2 T cells has been developed over the past decade. A large number of clinical trials have been conducted on various types of solid tumors as well as hematological malignancies. Vγ9Vδ2 T cell-based immunotherapy can be classified into two categories based on the methods of activation and expansion of these cells. Although the in vivo expansion of Vγ9Vδ2 T cells by phosphoantigens or nitrogen-containing bisphosphonates (N-bis) has been translated to early-phase clinical trials, in which the safety of the treatment was confirmed, problems such as activation-ind

Lost in transcription: molecular mechanisms that control HIV latency.

Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover,

Modulating CD8⁺ T cell immunity through exercise: mechanistic insights and implications for precision immunotherapy.

CD8⁺ T lymphocytes are pivotal effectors of adaptive immunity, executing cytotoxic mechanisms essential for pathogen clearance, tumor surveillance and tissue protection. Their activity is shaped by antigenic stimulation, cytokine networks and the metabolic and structural architecture of the tissue microenvironment. Physical exercise has emerged as a potent, non-pharmacological modulator of CD8⁺ T cell biology, capable of influencing recruitment, activation, differentiation and functional persistence. Acute exercise mobilizes effector and memory subsets, enhances trafficking to peripheral tissu

Multiple Myeloma: An Overview of the Current and Novel Therapeutic Approaches in 2020.

The survival rate of multiple myeloma (MM) patients has drastically increased recently as a result of the wide treatment options now available. Younger patients truly benefit from these innovations as they can support more intensive treatment, such as autologous stem cell transplant or multiple drug association (triplet, quadruplet). The emergence of immunotherapy allowed new combinations principally based on monoclonal anti-CD38 antibodies for these patients. Still, the optimal induction treatment has not been found yet. While consolidation is still debated, maintenance treatment is now well