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Multiple Myeloma Therapy: Emerging Trends and Challenges.

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergenc

Lipid nanoparticle-mediated mRNA/siRNA dual-bioengineered dendritic cell vaccines combined of PD-1/PD-L1 blockade for boosting tumor immunotherapy.

DC vaccines occupy a pivotal position in the realm of cancer treatment, leveraging the immune system to precisely target and effectively eliminate tumor cells. However, current challenges in tumor DC vaccine development include issues such as limited efficacy and potential upregulation of immunosuppressive molecules like PD-L1 on tumor cells. Herein, we employed microfluidic technology to fabricate lipid nanoparticles (LNPs) that simultaneously encapsulate OVA mRNA (mOVA), encoding the model antigen OVA, and siRNA targeting PD-L1. The LNP/mOVA/siPD-L1 nanoparticles were utilized to transfect b

CAR T-cell therapy in mature lymphoid malignancies: clinical opportunities and challenges.

The advent of chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment paradigm of various hematologic malignancies. Ever since its first approval for treatment of acute lymphoblastic leukemia (ALL) in 2017, CAR T-cell therapy has been found to be efficacious in various other lymphoid malignancies, with recent approvals in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Although CAR T-cell therapeutics offer a novel immunotherapeutic approach to treat otherwise refractory malignancies, the plethora of studies/products and complexities in manu

Bispecific Antibodies and CAR T in Multiple Myeloma: Appropriate Selection of Patients and Sequencing.

T-cell redirecting therapies (TCR) marked a step forward in the treatment of relapsed/refractory multiple myeloma (RRMM). These agents, represented by chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs), proved to ameliorate the prognosis of difficult-to-treat patients in pivotal clinical trials, leading to their introduction into clinical practice. Both strategies rely on recruiting patients' T-cells against specific tumor antigens, with B-cell maturation antigen (BCMA) and G-protein coupled receptor group C family 5 member D (GPRC5D) being the targets most extensively s

Помимо CAR-T: Предотвращение и лечение релапса в гематологических злодеяниях B-Cell.

Цимерическая антигенная лейкемия (КАР) Т-клетотерапия произвела революцию в области лечения рентгеновской/рефракторной (R/R) острой лимфоболической лейкемии (B-LAL), неходгкинской лимфомы (NHL) и множественной миеломы (MM); однако значительная часть пациентов в конечном итоге, несмотря на первоначальные ответные меры, вновь заболела. В настоящем обзоре содержится краткий обзор клеточной терапии CAR-T, включая ее производственный процесс и связанные с этим токсичные свойства, до изучения биологических механизмов, лежащих в основе рецидива после CAR-T в B-ALL, NHL-особенно большой лимфомы B-клет

The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers.

Purpose of reviewWe aim to review the most recent findings in the use of NK cells in childhood cancers.Recent findingsNatural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less li

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, December 5th 2015

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The 48th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Poster Session (P001 - P578).

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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

Phase Ib, multicentre, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneously administered mosunetuzumab in participants with systemic lupus erythematosus.

OBJECTIVE: To determine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of subcutaneously administered mosunetuzumab, a CD20xCD3 T-cell-engaging bispecific antibody, in participants with systemic lupus erythematosus (SLE). METHODS: This phase Ib, multicentre, open-label, dose-escalation study enrolled 15 participants diagnosed with active autoantibody-positive SLE, demonstrated by an SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥4 at screening. The study included two fixed-dosing dose-finding cohorts (1.6 mg or 5 mg of mosunetuzumab on day 1) and three step-up d

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

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Совпадение в полном тексте источника
… GVHD is mediated by antigen-specific TCRαβ, thus targeting genes related to the expression of the TCRαβ/CD3 complex can disrupt its cell surface expression at the genomic level [ 5 ]. …

The investigation of oncolytic viruses in the field of cancer therapy.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in

:: 45th Ежегодное совещание Европейского общества по трансплантации крови и костного мозга: Врачи - сессия плаката.

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BCMA-targeted immunotherapy for multiple myeloma.

B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as

Fine-Tuning through Generations: Advances in Structure and Production of CAR-T Therapy.

Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target m

Совпадение в полном тексте источника
… The optimal antigen response of chimeric antigen receptors harboring the CD3zeta transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex J. Immunol. 2010 184 6938 6949 10.4049/jimmunol.0901766 20483753 118. Muller Y.D. Nguyen D.P. Ferreira L.M.R. …

Gut microbiota deficiency ameliorates multiple myeloma and myeloma-related bone disease by Th17 cells in mice models.

Purpose: Multiple myeloma, the second most common hematological tumor, is currently incurable. Multiple myeloma-related bone disease is a characteristic clinical symptom that seriously affects the survival and prognosis of patients. In recent years, gut microbiota has been shown to play an important role in the occurrence and development of multiple myeloma. However, whether and how it affects the development of myelomatous bone disease is unclear. Methods: To investigate the mechanism and influence of the microbiota on multiple myeloma and myeloma bone disease, a myeloma-gut microbiota deleti

Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years and provides new opportunities to treat HCC. However, HCC has various etiologies and can evade the immune system through multiple mechanisms. With the rapid development of genetic engineering and synthetic biology, a variety of novel immunotherapies have been employed to treat advance

CD38 Is Robustly Induced in Human Macrophages and Monocytes in Inflammatory Conditions.

Macrophages and their monocyte precursors mediate innate immune responses and can promote a spectrum of phenotypes from pro-inflammatory to pro-resolving. Currently, there are few markers that allow for robust dissection of macrophage phenotype. We recently identified CD38 as a marker of inflammatory macrophages in murine in vitro and in vivo models. However, it is unknown whether CD38 plays a similar marker and/or functional role in human macrophages and inflammatory diseases. Here, we establish that CD38 transcript and protein are robustly induced in human macrophages exposed to LPS (±IFN-γ)

Проблемы с многократной терапией миеломы у пациентов постарше и посторонних.

Каждый год больше, чем 150,000 во всем мире диагностируются случаи множественной миеломы (ММ) и более 100,000 Зарегистрированы случаи смерти в результате этого злонамеренного поведения. Уровень заболеваемости ММ растет во всем мире, особенно в странах с высоким уровнем дохода и среди мужского населения в возрасте ≥ 50. Хотя прогресс в осуществлении стратегий лечения привел к повышению уровня выживания за последние десятилетия, ММ остается неизлечимым во многих случаях. Важно то, что one- треть пациентов с диагнозом MM - >75 возраст и характеризуется относительно низкой трудоспособностью или сл