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Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematological tumor originating from the precursor of plasmacytoid dendritic cells (pDCs) with a persistent and progressive course of illness. Despite being an aggressive disease BPDCN has an initial indolent course manifested as skin lesions. Alongside or following the skin lesion, the extra-cutaneous manifestation develops and includes lymphadenopathy, splenomegaly, and hepatomegaly. The BPDCN diagnosis is mainly based on the immunophenotype.  Herein, we report the case of a 72-year-old male patient who presented with a hist

Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies.

Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) cases. B-cell maturation antigen (BCMA) is a key target for novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs), which vary in efficacy, toxicity, and accessibility. To compare the efficacy and safety of BCMA-directed CAR-T therapies and BiTEs in R/R MM through a systematic review and meta-analysis. We systematically searched PubMed, Embase, and the Cochrane Library up to October 2, 2024, for studies evaluating BCM

Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice.

BackgroundGlioblastoma (GB), the most aggressive brain cancer, remains a critical clinical challenge due to its resistance to conventional treatments. Here, we introduce a locoregional targeted-α-therapy (TAT) with the rat monoclonal antibody 9E7.4 targeting murine syndecan-1 (SDC1) coupled to the α-emitter radionuclide astatine-211 (211At-9E7.4).MethodsWe orthotopically transplanted 50,000 GL261 cells of murine GB into the right striatum of syngeneic female C57BL/6JRj mice using stereotaxis. After MRI validation of tumour presence at day 11, TAT was injected at the same coordinates. Biodistri

The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial.

Myeloid Derived suppressor cells (MDSCs) play a key role in the progression and recurrence of human malignancies and in restraining the efficacy of adjuvant therapies. We have previously shown that Tadalafil lowers MDSCs and regulatory T cells (Treg) in the blood and in the tumor, primes a tumor specific immune response, and increases the number of activated intratumoral CD8+T cells in patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC). However, despite these important immune modulatory actions, to date no clinically significant effects have been reported following PDE5 inhibi

Primary cutaneous lymphomas: diagnosis and treatment.

Primary cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative neoplasms, with lymphatic proliferation limited to the skin with no involvement of lymph nodes, bone marrow or viscera at the diagnosis. Cutaneous lymphomas originate from mature T-lymphocytes (65% of all cases), mature B-lymphocytes (25%) or NK cells. Histopathological evaluation including immunophenotyping of the skin biopsy specimen is the basis of the diagnosis, which must be complemented with a precise staging of the disease and identification of prognostic factors, to allow for the choice of the best treat

Improving Biologics' Effectiveness in Clinical Oncology: From the Combination of Two Monoclonal Antibodies to Oligoclonal Antibody Mixtures.

Monoclonal antibodies have revolutionized the treatment of many diseases, but their clinical efficacy remains limited in some other cases. Pre-clinical and clinical trials have shown that combinations of antibodies that bind to the same target (homo-combinations) or to different targets (hetero-combinations) to mimic the polyclonal humoral immune response improve their therapeutic effects in cancer. The approval of the trastuzumab/pertuzumab combination for breast cancer and then of the ipilimumab/nivolumab combination for melanoma opened the way to novel antibody combinations or oligoclonal a

Expression of the TIGIT axis and the CD39/CD73 purinergic pathway in bone metastasis-derived immune cells.

BackgroundBone metastases (BM) represent one of the most common sites of metastasis. The study aimed to compare the composition of immune cell infiltration from aspirates of different BM prior to systemic therapy.MethodPhenotypic and functional analyses were conducted via multiparametric flow cytometry (MFC) on BM-derived aspirates obtained from patients with breast cancer (BC, n = 6), patients with prostate cancer (PC, n = 5), patients with non-small-cell lung cancer (NSCLC) (n = 7), patients with myeloma (MM, n = 10) and bone aspirates from age-matched non-malignant controls (NMC, n = 10).Re

Clinical Management of Triple-Class Refractory Multiple Myeloma: A Review of Current Strategies and Emerging Therapies.

Major progress has been made in the upfront treatment of multiple myeloma, but the disease ultimately relapses and leads to death in the vast majority of those afflicted. New treatment strategies and modalities are necessary to treat myeloma in relapse, particularly in cases of triple-refractory status defined by disease progression during or shortly after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibody therapy. In this manuscript, we review recent promising developments in the treatment of triple-class refractory myeloma including bispecific an

Safety and Efficacy of Bispecific Antibody Treatment in Relapsed/Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis of Proportions from Clinical Trials.

Background: Multiple myeloma (MM) is an incurable plasma cell dyscrasia with particularly adverse prognosis in relapsed, multi-drug refractory settings. The management of those patients is challenging as treatment options are limited. In this context, bispecific antibodies (BsAbs) have recently emerged as promising therapeutic agents, and several have gained regulatory approval. To better understand their impact in MM landscape, we performed a systematic review and meta-analysis assessing their efficacy and safety in patients with relapsed/refractory MM (RRMM). Methods: A systematic search was

Integrated Engineering of CAR-T Cells for Solid Tumours.

Chimeric antigen receptor (CAR) T-cell therapy has achieved durable efficacy in hematologic malignancies but encounters persistent obstacles in solid tumours, including antigen heterogeneity, a suppressive tumour microenvironment (TME), and intrinsic T-cell dysfunction. This review examines the transition from single-axis engineering to an integrated framework that addresses these hurdles in sequence. We delineate how next-generation CAR-T cells are designed for precise spatiotemporal activation through logic-gated and pharmacologically regulatable receptors, while being reinforced by metaboli

Elrexfio™ (elranatamab-bcmm): The game-changer in treatment of multiple myeloma.

Multiple myeloma is the second most common plasma cell malignancy, characterized by uncontrolled proliferation of plasma cells within the bone marrow. ELREXFIO™ (elranatamab-bcmm) is a recently FDA-approved drug for relapsed and refractory multiple myeloma. The progression of multiple myeloma involves interactions with various bone marrow cell types, and targeting this microenvironment has shown promising results in inhibiting its growth and osteolysis. ELREXFIO, a bispecific antibody targeting CD3 and BCMA, activates cytotoxic T-lymphocyte responses against BCMA-expressing myeloma cells. Clin

Регулирование пациентов с реанимированными/реферантными миеломами, лечившимися с Талкетамабом: основные моменты из точки зрения фармацевтов.

Talquetamab — семейство рецепторов с белковым белком в классе G. 5 член D (GPRC5D) и CD3-targeting bi специфическая антитела с > 71% :: общее реагирование пациентов с рецидивной или рефрактной множественной миеломой, three другие виды наркотиков. GPRC5D сильно отражается на клетках миэломы, а также некоторое выражение в обычных волосатых фолликах, коже и языке. Его уникальное выражение на этих нормальных тканях приводит к явной структуре неблагоприятных явлений (АЭ), как это было отмечено на этапе I/II. MonumenTAL-1 суд. GPRC5D-related АО включали оральные побочные эффекты (например, дисгейсия

Antibacterial prophylaxis and antimicrobial stewardship in the era of innovative therapies for haematological malignancies: transplantation, cellular therapies and new drugs.

Antibacterial prophylaxis has long been a cornerstone of supportive care in patients with haematological malignancies undergoing intensive chemotherapy and haematopoietic stem cell transplantation (HSCT), particularly in the setting of prolonged and profound neutropenia. However, the widespread use of fluoroquinolone (FQ) prophylaxis has increasingly raised concerns related to antimicrobial resistance, microbiota disruption, drug-related toxicity, and Clostridioides difficile infection, challenging its universal application. At the same time, the therapeutic landscape of haematology is rapidly

The utility of stereotactic biopsy of intracranial lesions in the diagnosis of leukemia complicated by central nervous system lesions.

BACKGROUND: Leukemia complicated by central nervous system (CNS) lesions (LCNSL) includes leukemia involving the CNS (CNSL) and CNS secondary lesions related to leukemia treatment (e.g., CNS infections, leukoencephalopathy, inflammatory demyelination, and vascular diseases). The clinical manifestations and imaging characteristics of different types of LCL are similar, increasing the possibility of misdiagnosis. This study aimed to enhance our understanding and management of LCL. METHODS: We retrospectively collected clinical data from 22 patients with LCL and analyzed their magnetic resonance

The current socioeconomic and regulatory landscape of immune effector cell therapies.

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T ce

Chemorefractory extranodal nasal-type natural-killer/T-cell lymphoma with great response to pembrolizumab in a young patient: a case report.

IntroductionExtranodal, natural-killer/T-cell lymphoma of nasal type is a rare but aggressive disease usually presenting as progressive necrotic lesions in the nasal cavity that responds poorly to chemotherapy. In this paper, we report a relapsing, chemorefractory case of extranodal natural-killer/T-cell lymphoma responding to checkpoint inhibitor immunotherapy with pembrolizumab.Case presentationA 32-year-old Hispanic woman with a history of recurrent sinusitis and preseptal abscess presented with a hoarse voice, swelling around the right eye, and diplopia. Laryngoscopy showed infiltrating ti

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe.

Chimeric antigen receptor (CAR)-T cell therapy is a new class of cellular immunotherapies that involves ex vivo genetic modification of T cells to incorporate an engineered CAR. After infusion into the patient, the CAR-expressing T cells recognize specific tumor targets and induce an immune response against them. The technology utilized is fundamentally different from previously available cancer treatments. Currently, most CAR-T cell therapies use autologous T cells. Tisagenlecleucel (formerly CTL019) is an anti-CD19 CAR-T cell therapy that was recently approved in the United States for the tr

Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, trigg

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer.

Although normally restricted to activated T and B cells and mature dendritic cells, constitutive expression of CD70, a member of the tumor necrosis family, has been described in both hematological and solid tumors, where it increases tumor cell and regulatory T cell survival by signaling through its receptor, CD27.We have assessed the co-expression of CD70 and CD27 in non-small cell lung cancer (NSCLC) by immunohistochemistry to explore a correlation between expression of the protein and tumor histologic subtype, genetic aberrations and prognosis. Furthermore, we tested the ability of ARGX-110

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… A soluble form of the human T cell differentiation antigen CD27 is released after triggering of the TCR/CD3 complex. J Immunol. 1991;147:29–35. 19. Kok M, Bonfrer JM, Korse CM, de Jong D, Kersten MJ. …