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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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… Future perspectives Co-stimulation CAR-induced T-cell activation requires T-cell receptor (TCR) signalling through the CD3 complex (signal 1) and costimulatory CD28 signalling (signal 2). …

Case report: CD8 positive T-cell Prolymphocytic Leukemia presenting complex karyotype with a rare chromosomal abnormality der(2)t(1;2)(q21;q37) and additional signals of the genes MYC, IGH, and TP53.

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Immunotherapy in chronic lymphocytic leukemia: advances and challenges.

Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition is marked by an accumulation of lymphocytes within the peripheral blood, bone marrow, spleen, and lymph nodes. The associated immune dysregulation predisposes CLL patients to a higher risk of secondary malignancies and infections, which significantly contribute to morbidity and mortality rates. The advent of immunotherapy has revolutionized the prognosis of CLL, advancing treat

Different expression patterns of VISTA concurrent with PD-1, Tim-3, and TIGIT on T cell subsets in peripheral blood and bone marrow from patients with multiple myeloma.

V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is considered as an immunosuppressive factor and potential therapeutic target for anticancer therapy. However, little is known about VISTA expression and its role in immunosuppression in multiple myeloma (MM). In this study, VISTA expression and co-expression with programmed cell death receptor-1 (PD-1), T cell immunoglobulin mucin-domain-containing-3 (Tim-3), and T cell immunoglobulin and ITIM domain (TIGIT) in CD3+, CD4+, CD8+, and regulatory T (Treg) cells were analyzed in patients with MM by multi-color fluores

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma.

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CA

Bispecific antibodies: unleashing a new era in oncology treatment.

Advancements in diagnostic and therapeutic standards have substantially enhanced the survival of patients with malignant tumors. Nevertheless, the quest for effective strategies to address resistant or recurrent advanced tumors remains a critical and unwavering objective. Bispecific antibodies (BsAbs) unleashed a new era of anti-tumor treatment by simultaneously binding to two distinct targets, thereby enhancing specificity, minimizing off-target toxicities, and synergistically modulating anti-tumor immunity and the tumor microenvironment. Compared with the combination of two monoclonal antibo

Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.

Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, i

Stepping forward: T-cell redirecting bispecific antibodies in cancer therapy.

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T

Nephrotoxicity in Bispecific Antibodies Recipients: Focus on T-Cell-Engaging Bispecific Antibodies.

Recently, bispecific antibodies (BsAbs) are evolving the landscape of cancer treatment and have significantly improved the outcomes of relapsed or refractory cancer patients. As increasing BsAbs entered clinical practice, specific toxicities have emerged, and renal side-effects have been described. However, there are a lack of studies analyzing the nephrotoxicity in the anti-cancer BsAbs recipients systematically. In this review, we demonstrate the etiologies, mechanisms, other risk factors and treatment options of kidney injury in the BsAbs recipients to provide a more comprehensive insight i

8(th) Annual European Antibody Congress 2012: November 27-28, 2012, Geneva, Switzerland.

The 8th European Antibody Congress (EAC), organized by Terrapin Ltd., was again held in Geneva, Switzerland, following on the tradition established with the 4th EAC. The new agenda format for 2012 included three parallel tracks on: (1) naked antibodies; (2) antibody drug conjugates (ADCs); and (3) bispecific antibodies and alternative scaffolds. The meeting started and closed with three plenary lectures to give common background and to share the final panel discussion and conclusions. The two day event included case studies and networking for nearly 250 delegates who learned of the latest adva

From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis despite advances in treatment strategies. Standard treatment regimens induce remissions in many patients, but relapse occurs in approximately half, highlighting the urgent need for novel therapeutic strategies. Antibody-based therapies have significantly improved the treatment of acute lymphoblastic leukemia (ALL), but progress in AML has been slower, with only gemtuzumab ozogamicin (GO) receiving FDA approval to date. This is largely due to the absence of AML-specific surface antigens and the challeng

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation.

BackgroundT-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (MethodsReview of 55 phase I-III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data.ResultResponse rates now approach ~40% in selected settings, marking an inflection point. In extensive

Bispecific antibodies in the treatment of epithelial ovarian, endometrial, and cervical cancer: an overview of current applications, challenges, and emerging opportunities.

Gynecological cancer remains one of the leading causes of mortality worldwide. Recent advances in genomic and molecular sequencing have significantly enhanced our understanding of the biological pathways that drive tumor progression and resistance to therapy. Targeted therapies, including monoclonal antibodies (mAbs), have revolutionized cancer treatment by selectively interfering with oncogenic proteins expressed on cancer cells. However, the long-term clinical benefit is often limited due to the emergence of drug resistance, frequently mediated by compensatory signaling pathways or immune es

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of

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… Mechanism of action TCEs have dual specificities, a characteristic that allows them to simultaneously bind to the CD3 complex on T cells and a target antigen on tumors [ 44 ]. …

Всеобъемлющая оценка неблагоприятных профилей, связанных с биконкретными антителами в множестве миеломы.

Биотечные антитела (BSAbs) сулили большие надежды в борьбе с повторной/охлажденной множественной миеломой (MM). Несмотря на свою эффективность, этот класс наркотиков связан со значительными токсичными свойствами. В этом исследовании мы провели совместный анализ имеющихся клинических испытаний БСАБ для лечения ММ, включая полные публикации и резюме до апреля 2025. BsAb были отнесены к категории two группы: антигены созревания клеток B (BCMA) и GPRC5D/FcRH5 BsAbs. Тест Welch был проведен для сравнения характеристик безопасности каждого агента. Для кластеризации мы использовали анализ основных ко

Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells

The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.

The advent of cancer immunotherapy has fundamentally restructured the oncological paradigm, moving away from agents that directly target tumor cell kinetics toward strategies that empower the host immune system to recognize and eliminate malignancy. Central to this revolution is the cytotoxic T lymphocyte (CTL), now harnessed as a potent "living drug" through engineered and naturally selected modalities. This review provides a critical, in-depth examination of the three dominant pillars of T cell-driven therapies: Chimeric Antigen Receptor T-cell (CAR-T) therapy, Tumor-Infiltrating Lymphocyte

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

Природные клетки убийцы в множестве склерозов: враги или друзья?

Множественный склероз (MS) — иммунное расстройство, связанное с центральной нервной системой (CNS), в которой происходит демиэлизация. Считается, что инициирование и прогрессирование MS в значительной степени зависят от CD4+T лимфоцитов, однако новые данные подчеркивают участие врожденной иммунной системы в реакции на болезни MS. В целом некоторые виды иммунных клеток играют определенную роль, при этом существенно важное значение имеют клетки естественного убийцы (НК). В ходе аутоиммунной болезни, как, например, MS, различные подвиды клеток естественного убийцы функционируют по-разному. У люде

Механистические понимания и достижения биконкретной T-клетки, использующей антителную терапию в мультимиеломе.

Множественная миелома (ММ) — клональная порча неизмеримо дифференцированных плазменных клеток, характеризующаяся инфильтрацией костного мозга и чрезмерным производством моноклонных иммуноглобулинов, что приводит к повреждению конечной формы, например остеолитических повреждений костей. Несмотря на значительный терапевтический прогресс, достигнутый с протеаозными ингибиторами, иммуномодуляционными препаратами и anti-CD38 Моноклональные антитела, множественная миелома остаются неизлечимыми, а результаты для трехклассных пациентов-восстановителей остаются мрачными, при этом медиана выживаемости н

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… The engagement of the CD3 complex triggers synapse formation and phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs) on the CD3ζ chain, recruiting Src-family kinases such as lymphocyte-specific protein tyrosine kinase (Lck) and initiating downstream signaling cascades via zeta-chain-associated …