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CAR T-Cells in Multiple Myeloma Are Ready for Prime Time.

The survival of patients with multiple myeloma (MM) has been dramatically improved in the last decade thanks to the incorporation of second-generation proteasome inhibitors (PI), immunomodulatory drugs (IMID), and, more recently, anti-CD38 monoclonal antibodies (MoAb). Nevertheless, still, a major proportion of MM patients will relapse, underscoring the need for new therapies in this disease. Moreover, survival in patients failing the current standard of care regimens (including PI, IMIDs, and anti-CD38 MoAb), which is now defined as triple-class refractory, remains dismal, and new drugs with

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… Moreover, the class I major histocompatibility complex (MHC I) is also knock out using CRSPR/Cas 9 [ 47 ]. A phase I trial using CTX120 in RRMM is ongoing ( NCT04244656 ). …

Visualizing immunotherapy for multiple myeloma worldwide from 2013 to 2023: A bibliometric analysis.

Multiple myeloma (MM) is a malignant, clonal proliferative disease of plasma cells that remains incurable. This paper aims to analyze the current research status and emerging trends in immunotherapy for MM through bibliometric methods, thereby providing valuable references and guidance for future research and clinical practice. This study presents a bibliometric analysis of 1,018 English-language publications related to MM immunotherapy, which were published in the Web of Science (WoS) Core Collection database from 2013 to 2023. VOSviewer and CiteSpace were employed to visualize the research h

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… I In MM therapy, bispecific antibodies target specific molecules on malignant plasma cells and CD3 on T cells, activating T cells independently of the major histocompatibility complex and T cell receptor specificity. 37 , 38 This innovative approach directly activates T cells and triggers tumor cell …

Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.

Aging is associated with a decline in immune function, termed immunosenescence, which compromises host defences and increases susceptibility to infections and cancer. Physical exercise is widely recognized for its myriad health benefits, including the potential to modulate the immune system. This review explores the bidirectional relationship between immunosenescence and physical exercise, focusing on their interplay in shaping antitumor immunity. We summarize the impact of aging on innate and adaptive immune cells, highlighting alterations that contribute to immunosenescence and cancer develo

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… This decline predominantly stems from the reduced expression of major histocompatibility complex class II (MHC-II) molecules, particularly the human leukocyte antigen (HLA)-DR isotype 37 . Efferocytosis, which refers to the phagocytic removal of apoptotic cells, has been shown to decline with age. …

Current progress in CAR-based therapy for kidney disease.

Despite significant breakthroughs in the understanding of immunological and pathophysiological features for immune-mediated kidney diseases, a proportion of patients exhibit poor responses to current therapies or have been categorized as refractory renal disease. Engineered T cells have emerged as a focal point of interest as a potential treatment strategy for kidney diseases. By genetically modifying T cells and arming them with chimeric antigen receptors (CARs), effectively targeting autoreactive immune cells, such as B cells or antibody-secreting plasma cells, has become feasible. The emerg

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… Initial CD4+ T cells recognize major histocompatibility complex class II (MHC-II), which is presented by antigen-presenting cells (APCs), initiating cellular immunity and expressing high-affinity receptors for interleukin (IL)-2. …

Adoptive immune cell therapy for colorectal cancer.

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide, with limited options for patients at advanced stages. Immunotherapy, particularly immune cell-based therapies, has gained significant attention as an innovative approach for targeting CRC. This review summarizes the progress in various immune cell therapies, including DC vaccine, CAR/TCR-T cells, CAR-NK cells et al, each engineered to recognize and attack cancer cells expressing specific antigens. CAR-T cell therapy, which has been successful in hematologic cancers, faces challenges in CRC due to the

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… Briefly, these cells share functional and phenotypic properties with NKT, NK and T cells and are characterized by rapid expansion ex vivo, non-major histocompatibility complex (MHC)-restricted tumor-killing activity, strong antitumour activity and minimal toxicity. …

Oncolytic Viruses for Cancer Therapy in Dogs.

Cancer remains the leading cause of death in domestic dogs. Conventional therapeutic approaches, including surgery, chemotherapy, and radiotherapy, frequently fail to achieve sustained remission or stabilization. Oncolytic virotherapy, a rapidly advancing therapeutic modality in human oncology, is emerging as a novel strategy in veterinary medicine. This systematic review summarizes current knowledge on the application of oncolytic viruses (OVs) in canine cancer treatment, focusing on their mechanisms of action, safety profiles, and clinical efficacy. We evaluate diverse OV platforms, includin

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… Coxsackie B and adenovirus receptor, integrin and major histocompatibility complex class I expression in human prostate cancer cell lines: Implications for gene therapy strategies Prostate Cancer Prostatic Dis. 2003 6 6 11 10.1038/sj.pcan.4500611 12664058 85. Uotani K. Tazawa H. Hasei J. …

Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma.

Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors. Furthermore, there was no evidence that MAIT cells accumulated at the disease site (bone marrow) of t

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… Tilloy F An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha/beta T cell subpopulation in mammals The Journal of experimental medicine 1999 189 1907 1921 10.1084/jem.189.12.1907 10377186 PMC2192962 17. …

The Role of Gamma Delta T Lymphocytes in Physiological and Pathological Condition-Focus on Psoriasis, Atopic Dermatitis, Autoimmune Disorders, Cancer and Lymphomas.

Gamma delta (γδ) T cells are a heterogeneous population of cells that play roles in inflammation, host tissue repair, clearance of viral and bacterial pathogens, regulation of immune processes, and tumor surveillance. Recent research suggests that these are the main skin cells that produce interleukin-17 (I-17). Furthermore, γδ T cells exhibit memory-cell-like characteristics that mediate repeated episodes of psoriatic inflammation. γδ T cells are found in epithelial tissues, where many cancers develop. There, they participate in antitumor immunity as cytotoxic cells or as immune coordinators.

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… γδ T cells are innate lymphocytes, unrestricted by the major histocompatibility complex (MHC). They have a larger number of antigen receptors compared with cells with αβ T cells [ 5 ]. 2. …

Механистическая взаимосвязь между множественной миеломой и тяжелой SARS-CoV-2 Инфекция: терапевтическое обещание месенхимальных стволовых ячеек с внешней клеткой.

Пациенты с множественной миеломой (ММ) демонстрируют глубокое иммунное регулирование, предвосхищая их до тяжелых результатов после SARS-CoV-2 инфекция. Текущие данные свидетельствуют о наличии общих иммунопатологических механизмов, связывающих ММ и COVID-19, с уделением особого внимания interleukin-6 (В тыс.IL-6) ось как общий усилитель воспаления, а не как единственный движитель болезни. Для ММ характерна исходная провоспалительная среда, частично обусловленная: IL-6, которая еще больше усиливается в течение SARS-CoV-2 Инфекция, приводящая к эскалации цитокина, дополняет активацию, коагулопат

Exploring the Emerging Association Between Immune Checkpoint Inhibitors and Thrombosis.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their association with thrombosis presents significant clinical challenges. Patients with cancer already exhibit elevated risks for venous thromboembolism and arterial thrombosis, with treatment modalities like chemotherapy further exacerbating this risk. Emerging evidence suggests that ICIs contribute to thrombotic events through multifactorial mechanisms, including immune dysregulation, T cell activation, endothelial dysfunction, elevated tissue factor expression, and impaired fibrinolysis. Additional risk factors

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… ICI, immune checkpoint inhibitor; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; NET, neutrophil extracellular trap; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TCR, T cell receptor; TF, tissue factor. 3.1. …

Donor's age influences outcome in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide - a single center experience.

Haploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018-2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relap

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… Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ (2001) Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. …

Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneously primary hematopoietic neoplasm characterized by uncontrolled proliferation of immature myeloid cells, which is characterized with poor outcomes. Despite tremendous advances in the treatment paradigm of AML in the past several decades, the cure and prognosis remain unfavorable. More effective treatments are therefore needed to improve the clinical outcomes. Among newly emerging immunotherapies, chimeric antigen receptor (CAR)-T cell immunotherapy is an exceedingly promising approach that has remarkably improved the overall survival for patients

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… The reprogrammed T cells can specifically identify tumor-associated targets and destroy these cells without the assistance of the major histocompatibility complex ( 11 , 12 ). …

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

Биоинформатический анализ взаимодействия миелинов и микробов говорит о том, что в патогенезе множественных склерозов присутствуют различные виды молекулярной имитации.

Множественный склероз (MS) — разрушительная аутоиммунная болезнь, приводящая к разрушению милиновой оболочки в центральной нервной системе человека (КНС). Было установлено, что инфекция вирусов и бактерий тесно связана с наступлением мороза или его остротой. Мы предположили, что атака иммунной системы на милиновую оболочку может быть спровоцирована вирусами и бактериальными антигенами, которые напоминают компоненты миелиновой оболочки. Для выявления вирусных и бактериальных антигенов, похожих на миелин олигодендроцит гликпротеин (МОГ) и миелинский основной протеин (МБП), был применен подход, о

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… To assess the immunogenicity of these sequences and their effect on CD4+ T cells in the immune system, the obtained results were analyzed in the Immune Epitope Database (IEDB), which combines prediction methods for major histocompatibility complex (MHC) binding (using the 7-allele method) [ 46 ], and …

Endogenous immune recruitment in glioblastoma CAR T therapy: cytokine, myeloid, and chemokine circuitry.

BackgroundGlioblastoma (GBM) has remained relatively unresponsive to immunotherapy, with scattered durable responses reported in early CAR T-cell studies, but without clear benefit at the population level. The major challenge for GBM has been its heterogeneous nature with a significantly immunosuppressive microenvironment that is predominantly composed of myeloid cells, inhibiting T-cell infiltration, function, and providing a rapid pathway for adaptive resistance. The focus of this review is to reposition GBM CAR T-cell therapy as a systems-level issue, turning localized CAR T-cell cytotoxici

CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.

Several landmark studies over the past decade have uncovered a critical role of the CRL3KBTBD4 ubiquitin ligase complex in regulating stability of corepressor of repressor element 1 silencing transcription factor (CoREST) complex proteins and normal hematopoietic stem cell self-renewal. There is now mounting evidence that the CoREST complex plays oncogenic roles, although the contributions of its catalytic versus noncatalytic functions remain unclear. Here, we summarize and discuss mechanisms whereby the CoREST complex coopts tissue-specific transcription factors to elicit pathogenic activity

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… In SCLC, KDM1A expression is inversely correlated with expression of major histocompatibility complex class I (MHC-I) as well as antigen presentation pathway genes ( 122 ). …

Autoimmune Diseases and Plasma Cells Dyscrasias: Pathogenetic, Molecular and Prognostic Correlations.

Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part i

The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies.

Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In t

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… Unlike conventional TCRs, CARs recognize antigens independent of major histocompatibility complex (MHC) antigen presentation, avoiding the restriction of MHC molecules and solving the problem of tumor immune escape caused by the inhibition of MHC molecule expression [ 156 , 157 ]. … histocompatibility complex Akkermansia muciniphila Proton pump inhibitors Pancreatic ductal adenocarcinoma Myeloid-derived suppressor cells C-type lectin receptors Author contributions All authors have read and approved the article. …

Salvage therapy of multiple myeloma: the new generation drugs.

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and thera

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… On the other hand, myeloma cells upregulate class I antigen of the major histocompatibility complex (MHC) that are ligands for inhibitory killer immunoglobulin-like receptors (KIR) and in this way are able to avoid NK cell killing [ 43 ]. …

Bi- and Tri-specific antibodies in non-Hodgkin lymphoma: current data and perspectives.

Bispecific antibodies (BsAbs) are a new group of targeted therapies that are revolutionizing the treatment landscape of B-cell non-Hodgkin's lymphoma (B-NHL). In the relapsed/refractory setting, salvage chemotherapy and autologous stem cell transplantation are capable of curing 50% of patients, whereas the other half will have a dismal outcome with a median overall survival of less than 12 months. This unmet need reinforced the importance of innovative therapies like the BsAbs and CAR-T cell therapies. In this review, we delve into BsAbs in B-NHL from the preclinical development to clinical da

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… These T-cell engagers will bypass the major histocompatibility complex (MHC) leading to T-cell activation and tumor cell killing [ 13 ]. …