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Passive Monoclonal and Polyclonal Antibody Therapies

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Potential of gamma/delta T cells for solid tumor immunotherapy.

Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis

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… Recent research has elucidated the structures of two human γδ TCR-CD3 complexes and revealed their different assembly mechanisms. The Vγ5Vδ1 TCR-CD3 complex forms a dimeric structure that is critical for T cell activation. … In contrast, the Vγ9Vδ2 TCR-CD3 complex exists as a monomer with a flexible conformation, and the length of the bound peptide can modulate ligand binding and subsequent T cell activation ( 24 ). …

Therapeutic Antibodies for Myeloid Neoplasms-Current Developments and Future Directions.

Therapeutic monoclonal antibodies (mAbs) such as antibody-drug conjugates, ligand-receptor antagonists, immune checkpoint inhibitors and bispecific T cell engagers have shown impressive efficacy in the treatment of multiple human cancers. Numerous therapeutic mAbs that have been developed for myeloid neoplasms, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), are currently investigated in clinical trials. Because AML and MDS originate from malignantly transformed hematopoietic stem/progenitor cells-the so-called leukemic stem cells (LSCs) that are highly resistant to

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

CD28 Deficiency Ameliorates Blast Exposure-Induced Lung Inflammation, Oxidative Stress, Apoptosis, and T Cell Accumulation in the Lungs via the PI3K/Akt/FoxO1 Signaling Pathway.

Although CD28 is associated with the expression of inflammatory mediators, apoptosis-related protein, immunosuppression, and tumorigenesis, the effects of CD28 deficiency on blast exposure-induced lung injury have not been investigated. In this study, we have explored the effects of CD28 on blast exposure-induced lung injury and studied its potential molecular mechanisms. A mouse model of blast exposure-induced acute lung injury was established. Sixty C57BL/6 wild-type (WT) and CD28 knockout (CD28-/-) mice were randomly divided into control or model groups. Lung tissue samples were collected 2

Spinal Cord Compression As the Initial Manifestation of Relapsed Acute Myeloid Leukemia: A Case Report and Literature Review of a Rare Presentation.

Myeloid sarcoma (MS) is a solid mass of myeloid blasts outside the bone marrow (BM). Most cases occur in the setting of intramedullary acute myeloid leukemia (AML), but it can also present in the absence of overt BM disease, as a presentation of newly diagnosed or relapsed AML, or as a progression of myeloproliferative neoplasms or myelodysplastic syndromes. There are a few reports of spinal cord compression due to MS, and there is no consensus regarding its management. Here, we present a case of relapsed AML in the form of MS resulting in spinal cord compression and provide a comprehensive li

CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting.

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic acti

Нейроинфламмация в нейродегенеративных заболеваниях: сосредоточение внимания на посредничестве лимфоцитов T.

Нейродегенеративные заболевания представляют собой группу заболеваний, характеризующихся постепенным ухудшением центральной нервной системы, что приводит к снижению когнитивных, моторных и эмоциональных способностей пациентов. Нейроинфламмация играет важную роль в развитии этих заболеваний. Вместе с тем исследования терапевтических подходов к целенаправленной борьбе с нейроинфламмацией носят ограниченный характер. Все шире признается роль лимфоцитов, которые являются важнейшими посредниками адаптивной иммунной реакции, в нейродегенеративных заболеваниях. В настоящем обзоре основное внимание уд

The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma.

Multiple myeloma (MM) remains largely incurable despite enormous improvement in the outcome of patients. Over the past decade, we have witnessed the "era of monoclonal antibody (moAb)", setting new benchmarks in clinical outcomes for relapsed and newly diagnosed MM. Due to their excellent efficacy and relative safe toxicity profile, moAbs in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have become the new backbone of upfront anti-MM therapy. Yet, most patients will eventually relapse and patients who become refractory to IMiDs, PIs and moAbs have a dismal out

A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical

Dexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy strategies.

The glucocorticoid (GC) steroid dexamethasone (Dex) is used as a supportive care co-medication for cancer patients undergoing standard care pemetrexed/platinum doublet chemotherapy. As trials for new cancer immunotherapy treatments increase in prevalence, it is important to track the immunological changes induced by co-medications commonly used in the clinic, but not specifically included in trial design or in pre-clinical models. Here, we document a number of Dex -induced immunological effects, including a large-scale lymphodepletive effect particularly affecting CD4+ T cells but also CD8+ T

Targeting B-cell maturation antigen for treatment and monitoring of relapsed/refractory multiple myeloma patients: a comprehensive review.

Despite major therapeutic advancements in recent years, multiple myeloma (MM) remains an incurable disease with nearly all patients experiencing relapsed and refractory disease over the course of treatment. Extending the duration and durability of clinical responses will necessitate the development of therapeutics with novel targets that are capable of robustly and specifically eliminating myeloma cells. B-cell maturation antigen (BCMA) is a membrane-bound protein expressed predominantly on malignant plasma cells and has recently been the target of several novel therapeutics to treat MM patien

Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy.

Adoptive cellular immunotherapy (ACI) is a promising treatment for a number of cancers. Cytokine-induced killer cells (CIKs) are considered to be major cytotoxic immunologic effector cells. Usually cancer cells are able to suppress antitumor responses by secreting immunosuppressive factors. CIKs have significant antitumor activity and are capable of eradicating tumors with few side effects. They are a very encouraging cell population used against hematological and solid tumors, with an inexpensive expansion protocol which could yield to superior clinical outcome in clinical trials employing ad

Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, w

Advanced Diagnostic Techniques

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Мак-1 регулирует иммуноусилительное подавление конкретной стадии болезни через нитриковый путь в аутоиммунном заболевании.

Интегрин Мак-1 играет важнейшую роль в развитии множественного склероза (MS); однако лежащий в его основе механизм не в полной мере изучен. Здесь мы разработали мышь с миелоидной мышью Мак-1-дефицит. Используя экспериментальную аутоиммунную энцефаломиэлит (EAE) модель мыши MS, мы сообщаем, что Мак-1 на миелиоидных клетках является ключом к развитию болезней. Наши данные показывают, что миелиоидный Мак-1 значительно повышает интенсивность EAE и затрудняет регрессию заболеваний. Потеря Mac-1 увеличивает количество клеток Gr-1+ в периферийных тканях и CNS и предпочтительно ускоряет переход моноци

Hematological indices as indicators of silent inflammation in achalasia patients: A cross-sectional study.

Complete blood count (CBC)-derived parameters such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte (ELR) ratio, and platelet-to-lymphocyte ratio (PLR) are sensitive markers of occult inflammation and disease activity for systemic lupus erythematosus, rheumatoid arthritis, psoriasis, esophageal cancer, etc. We assessed NLR, PLR, MLR, and ELR as indicators of inflammation in achalasia patients.This cross-sectional study included 103 achalasia patients and 500 healthy blood donor volunteers (HD). Demographic, clinical and laboratory informatio

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one : National Harbor, MD, USA. 9-13 November 2016

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A Case Report Supporting the Use of Teclistamab in Multiple Myeloma With CNS Involvement.

Central nervous system involvement in multiple myeloma (MM-CNS) is a condition with poor prognosis and no clear treatment options. Standard regimens, including proteasome inhibitors (PIs) and immunomodulatory (IMiD) agents, provide minimal benefit in this setting, highlighting the need for novel therapies. Teclistamab, a bispecific T-cell engager (BiTE) targeting B-cell maturation agent (BCMA) and CD3, has demonstrated robust systemic activity in heavily pretreated MM but its role in CNS disease remains undefined, as patients with CNS involvement have been excluded from pivotal trials. We pres

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

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… By contrast, bispecific antibodies create a minimal adhesive bridge between two independent cells, relying on the native CD3 complex and the unmodified T cell signaling apparatus to transmit activation; the resulting synapse tends to be more transient and is repeatedly reformed as soluble engager molecules …