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T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.

T-cell engagers (TCEs) are a rapidly evolving class of cancer immunotherapies that redirect cytotoxic T cells to tumor-associated antigens independently of MHC presentation. This review outlines the development, structural formats, and therapeutic potential of various TCE platforms, including bispecific (BiTEs) and trispecific T-cell engagers (TriTEs), dual affinity re-targeting (DART), and other emerging formats. We also highlight the clinical success in treating hematologic malignancies as demonstrated by agents such as blinatumomab and teclistamab. We also discussed the ongoing challenges i

Инженерный антитела TACI × CD3 для перенаправления Т клеток на множественные миэломы.

Вышеупомянутые аббревиатуры, предназначенные для антигена созревания клеток В (BCMA), являющегося членом сверхсемейства суперрецептора некроза опухоли (TNFR), продемонстрировали замечательную клиническую эффективность в лечении рецидива/рефрактора множественной миеломы (MM). Вместе с тем одной из серьезных проблем является частое снижение регулирования или потеря выражения БКМА у пациентов, получающих иммунотерапию, ориентированную на БКМА, что существенно снижает терапевтическую эффективность и способствует прогрессированию и устойчивости к заболеваниям после первоначальной позитивной реакции

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… Antibody production and purification Balb/c mice (InVivos, Singapore) were immunized with DNA plasmids via hydrodynamic tail vein injection and hybridomas were generated as described previously. 36 Anti-hTACI antibody–producing clones were screened by flow cytometry using hTACI-HEK293T cells and subcloned …

Включаю T-камеры для очистки.

Те, кто занимается клетками, представляют собой преобразующий подход к иммунотерапии рака, стимулирующий использование двухуровневых и многообразных антителных конструкций для перенаправления китотоксичности Т-клеток на злокачественные клетки. Эти молекулы соединяют клетки Т и клетки опухоли, одновременно связывая CD3 с Т клетками и связанными с опухолью антигенами на раковые клетки, что позволяет точно определить иммунную направленность даже в иммунологических "холодных" опухолях. Последние достижения включают в себя условное использование Т-клеток, активированное микроэкологическими протезам

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in

Latest developments in MUC1 immunotherapy.

Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of appro

Immunotherapy in hematologic malignancies: achievements, challenges and future prospects.

The immune-cell origin of hematologic malignancies provides a unique avenue for the understanding of both the mechanisms of immune responsiveness and immune escape, which has accelerated the progress of immunotherapy. Several categories of immunotherapies have been developed and are being further evaluated in clinical trials for the treatment of blood cancers, including stem cell transplantation, immune checkpoint inhibitors, antigen-targeted antibodies, antibody-drug conjugates, tumor vaccines, and adoptive cell therapies. These immunotherapies have shown the potential to induce long-term rem

Development, efficacy and side effects of antibody‑drug conjugates for cancer therapy (Review).

Antibody-drug conjugates (ADCs) are anticancer drugs that combine cytotoxic small-molecule drugs (payloads) with monoclonal antibodies through a chemical linker and that transfer toxic payloads to tumor cells expressing target antigens. All ADCs are based on human IgG. In 2009, the Food and Drug Administration (FDA) approved gemtuzumab ozogamicin as the initial first-generation ADC. Since then, at least 100 ADC-related projects have been initiated, and 14 ADCs are currently being tested in clinical trials. The limited success of gemtuzumab ozogamicin has led to the development of optimization

Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy.

PurposeB-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma. However, the factors associated with prognosis following CAR T-cell therapy are unknown.Patients and methodsBetween July 1, 2018 and July 31, 2020, 61 patients with R/R multiple myeloma received anti-BCMA CAR T-cell therapy (Chictr.org number, ChiCTR1800017404). Step-wise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis-associated risk factors.ResultsSixty patients (98

Nuclear Heparanase Regulates Chromatin Remodeling, Gene Expression and PTEN Tumor Suppressor Function.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate and has been shown in various cancers to promote metastasis, angiogenesis, osteolysis, and chemoresistance. Although heparanase is thought to act predominantly extracellularly or within the cytoplasm, it is also present in the nucleus, where it may function in regulating gene transcription. Using myeloma cell lines, we report here that heparanase enhances chromatin accessibility and confirm a previous report that it also upregulates the acetylation of histones. Employing the Multiple Myeloma Research Foundation CoMMpass datab

Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study.

We report on the safety and immunogenicity of idiotypic DNA vaccination in a phase I, non-randomised, open-label study in patients with multiple myeloma. The study used DNA fusion gene vaccines encoding patient-specific single chain variable fragment, or idiotype (Id), linked to fragment C (FrC) of tetanus toxin. Patients in complete or partial response following high-dose chemotherapy and autologous stem cell transplant were vaccinated intramuscularly with 1 mg DNA on six occasions, beginning at least 6 months post-transplant; follow-up was to week 52. Fourteen patients were enrolled on study

Profile of elotuzumab and its potential in the treatment of multiple myeloma.

Although the introduction of novel drugs has improved outcome significantly in multiple myeloma (MM), many patients still eventually relapse. Monoclonal antibodies (mAbs) targeting MM-related antigens can complement currently available therapies. CS1 (also known as CD2 subunit 1, SLAMF7, CD319, and CRACC), a cell surface glycoprotein receptor that is a member of the signaling lymphocytic activation molecule (SLAM) family, is highly and nearly uniformly expressed in myeloma cells at the gene and protein level, but not expressed in other tissues, including hematopoietic stem cells, making CS1 a

Molecular Inhibitors of Growth Signals

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Ubiquitin and SUMO conjugation as biomarkers of acute myeloid leukemias response to chemotherapies.

Ubiquitin and the ubiquitin-like SUMO are covalently conjugated to thousands of proteins to modulate their function and fate. Many of the enzymes involved in their conjugation are dysregulated in cancers and involved in cancer cell response to therapies. We describe here the identification of biomarkers of the activity of these enzymes and their use to predict acute myeloid leukemias (AML) response to standard chemotherapy (daunorubicin-DNR and cytarabine-Ara-C). We compared the ability of extracts from chemosensitive and chemoresistant AML cells to conjugate ubiquitin or SUMO-1 on 9,000 prote

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

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… The discoveries of 1975 by George Köhler and César Milstein have opened the way for the production of several specific hybrid monoclonal antibodies specific to different antigens or cellular targets, obtained by the realization of hybridomas, resulting from the fusion of murine B lymphocytes and human … As previously mentioned, Köhler and Milstein ( 1975 ) revolutionized anti-cancer therapeutics with the development of hybridoma technology, used to produce monoclonal antibodies. Initially, the produced monoclonal antibodies were mouse antibodies. …

The Circular Life of Human CD38: From Basic Science to Clinics and Back.

Monoclonal antibodies (mAbs) were initially considered as a possible "magic bullet" for in vivo elimination of tumor cells. mAbs represented the first step: however, as they were murine in nature (the earliest experience on the field), they were considered unfit for human applications. This prompted the development of techniques for cloning the variable regions of conventional murine antibodies, genetically mounted on human IgG. The last step in this years-long process was the design for the preparation of fully human reagents. The choice of the target molecule was also problematic, since canc

Терапевтическое применение иммунобиологии в аутоиммунных и воспаленных заболеваниях.

Иммунобиологика или биологическая экспертиза революционизировали терапевтическую парадигму аутоиммунных и подстрекательских заболеваний путем выборочного целеопределения и модуляции дисрегулированных иммунных путей. По сравнению с обычными широкоспектральными иммунопрепрессантами биологика обеспечивает более конкретный и основанный на механизмах рациональный подход, зачастую связанный с повышением эффективности и сокращением неблагоприятных явлений. В этом обзоре содержится всеобъемлющий обзор репертуара терапевтической биологики, механизмов их действий, важнейших клинических испытаний и клини

Emerging new therapeutic antibody derivatives for cancer treatment.

Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells. The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies, such as antibody fragments, bispecific antibodies, and antibody derivatives (e.g., antibody-drug conjugates and immunocytokines). The miniaturization and multifunctionalization of antibodies are flexible and viable strategies for diagnosing or treating malignant tumors in a complex t

Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of persona

Immunogenicity to biological drugs in psoriasis and psoriatic arthritis.

Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the

Исправленный вариант: IL-12 p40 Monomer отличается от других IL-12 членов семьи на выборочно Inhibit IL-12Rβ1 Internalization and Concepting EAE.

Множественный склероз (MS) — самая распространенная болезнь человека, обезвоживающая CNS. Семья IL-12 состоит из четырех членов: IL-12 (p40:p35), IL-23 (p40:p19), p40 мономера (p40) и p40 гомодимера (p402). Поскольку все четыре члена содержат p40 в различных формах, важно использовать специальные моноклонные антитела (mAb) для характеристики этих молекул. Здесь, используя такой mAb, мы описываем выборочную потерю p40 в сыворотке пациентов с MS по сравнению со здоровым контролем. Аналогичным образом, мы также заметили сокращение p40 и увеличение IL-12, IL-23 и p402 в сыворотке мышей с экспериме