Результаты поиска

Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.

BackgroundCytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies.Main bodyCIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3-/CD56+ NK cells, and CD3+/CD56- cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary

Hematologic Malignancies: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Bispecific antibody targets and therapies in multiple myeloma.

Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation. While rates of cytokine release syndrome and neurotoxicity appear to be low

Letermovir does not affect long-term polyclonal immune reconstitution after allogeneic hematopoietic stem cell transplantation with ATG-based GvHD prophylaxis.

INTRODUCTION: Letermovir (LET) is an effective prophylaxis for human cytomegalovirus (HCMV) reactivations in HCMV-seropositive patients after allogeneic stem cell transplantation (allo-SCT). HCMV promotes polyfunctional T-cell responses, leading to HCMV-specific immune reconstitution (IR), thus contributing to polyclonal IR. METHODS: We retrospectively analyzed HCMV-seropositive patients undergoing allo-SCT with ATG-based GvHD prophylaxis to assess the impact of LET on timing and quality of polyclonal IR. Two cohorts were identified: a pre-emptive treatment (PET) historical cohort transplante

Teclistamab: First Approval.

Teclistamab (TECVAYLI®), a bispecific antibody that targets CD3 and B cell maturation antigen (BCMA), is being developed by Janssen Research and Development for the treatment of relapsed or refractory multiple myeloma. Teclistamab was recently granted conditional approval in the EU for the treatment of adult patients with relapsed and refractory multiple myeloma who have received three or more prior therapies (including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody) and have demonstrated disease progression on the last therapy. Teclistamab was subsequently approve

Immunotherapy of Multiple Myeloma: Promise and Challenges.

Whereas the treatment of MM was dependent solely on alkylating agents and corticosteroids during the prior three decades, the landscape of therapeutic measures to treat the disease began to expand enormously early in the current century. The introduction of new classes of small-molecule drugs, such as proteasome blockers (bortezomib and carfilzomib), immunomodulators (lenalidomide and pomalidomide), nuclear export inhibitors (selinexor), and histone deacetylase blockers (panobinostat), as well as the application of autologous stem cell transplantation (ASCT), resulted in a seismic shift in how

A guide to cancer immunotherapy: from T cell basic science to clinical practice.

The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regar

Advancing Immunotherapy in Chronic Lymphocytic Leukemia.

The treatment of chronic lymphocytic leukemia (CLL) has significantly shifted from chemoimmunotherapy to targeted therapies like Bruton's tyrosine kinase and BCL2 inhibitors. Despite these advancements, CLL remains an incurable disease characterized by immune dysregulation, therapeutic resistance, and cumulative toxicities. To overcome these challenges, novel immunotherapeutic strategies are emerging as fundamentally different approaches that target immune-tumor interactions. These innovations include novel monoclonal antibodies, bispecific antibodies that redirect T cell cytotoxicity, chimeri

Революции на передовой линии лечения миеломы: уроки и трудности в поиске лечения.

Множественная миелома (ММ) — рак костного мозга. За последние четверть века был создан заметный комплекс лечебных средств, которые проводят мероприятия по борьбе с миэломой с помощью различных механизмов и обеспечивают долговременную борьбу с болезнями у многих пациентов. Обнаружение того, что протеозные ингибиторы (ИП) и иммуномудуляторные препараты (ИМИД) нацелены на конкретные характеристики плазменных клеток, которые отражают биологию заболеваний и оказывают антимиеломную активность, привело к трансформативным изменениям в алгоритмах лечения. В последнее время появились достижения в област

Elranatamab: Механизм действий, клиническая и переводческая наука.

Elranatamab (ELREXFIO) — гуманизированный антитела, официально утвержденный для пациентов с несколькократной миеломой (RRMM). Elranatamab использует CD3 на Т клетках и B-клеточном антигене (BCMA) на клетках миэломы, чтобы вызвать цитолиз клеточного клеточного клетка с помощью Т. Рекомендуемая подкожная доза эльранатамб состоит из фиксированных доз увеличения 12 мг в день 1 и 32 мг в день 4 для снижения частотности и серьезности синдрома высвобождения цитокина (CRS), за которым следует полная фиксированная доза 76 мг один раз в неделю (QW) из недель 2 в адрес 24. В ответ, 76 мг QW уменьшается д

Case report: Cryoablation as a novel bridging strategy prior to CAR-T cell therapy for B cell malignancies with bulky disease.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a powerful immunotherapy in relapsed/refractory (R/R) hematological malignancies, especially in R/R B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). To prevent disease progression and reduce tumor burden during CAR-T cell manufacturing, bridging therapies prior to CAR-T cell infusion are crucial. At present, it has been demonstrated that targeted therapy, radiotherapy and autologous stem cell transplantation (ASCT) could serve as effective bridging strategies. However, whether cryoabl

Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients.

Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsivene

Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory netwo

Расширенный полиглутамин в ATAXIN1 приводит к потере функции, которая усугубляет остроту множественного склероза в модели мыши EAE.

Ataxin-1 (ATXN1) — белок, в котором расширение его полиглутаминового тракта вызывает нервно-дегенеративное расстройство спинномозговой системы 1 (SCA1) в результате повышения функциональности. Недавно было продемонстрировано, что АТXN1 дикая порода играет защитную роль в регулировании жесткости экспериментального аутоиммунного энцефаломиелита (EAE) — хорошо зарекомендовавшей себя модели мыши для мультиклероза (MS). В этом исследовании дополнительно изучается роль ATXN1 с расширенным полиглутаминым трактом в контексте MS с использованием модели мыши EAE.МЕТОДЫ: Гемизигиозные мыши Atxn1 (Atxn12Q

CAR-Based Cell Therapy in Head and Neck Cancer: A Comprehensive Review on Clinical Applicability.

Background/Objectives: Chimeric antigen receptor T-cell (CAR-T) therapy is a novel form of adoptive cellular immunotherapy that involves modifying autologous T cells to recognize and target tumor-associated antigens (TAAs) on malignant cells, independent of major histocompatibility complex (MHC) restriction. Although CAR-T therapy has shown remarkable success in treating hematologic malignancies, its efficacy in solid tumors remains limited, largely due to the lack of tumor-specific antigens and the complexity of the tumor microenvironment. This review aims to explore the rationale for continu

Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity.

BACKGROUND: Peripheral blood-derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential. MATERIALS AND METHODS: Pure cytokine activation and expansion of NK cells (super NK [SNK]) from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK

34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2 : National Harbor, MD, USA. 10 November 2019.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Targeted drug approvals in 2023: breakthroughs by the FDA and NMPA.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Chimeric Antigen Receptors Based on Low Affinity Mutants of FcεRI Re-direct T Cell Specificity to Cells Expressing Membrane IgE.

IgE is the key mediator of allergic responses. Omalizumab, an IgE-specific monoclonal antibody that depletes IgE, is effective for treating severe allergic asthma. The need for frequent administration of the expensive drug, however, limits its applications. Taking advantage of T cell memory, adoptive T cell therapy (ACT) targeting IgE-producing cells has the potential to achieve long-term suppression of IgE and relief of symptoms for severe allergic diseases. The transmembrane form of IgE (mIgE), which is present on all IgE-producing cells, serves as an excellent molecular target for ACT that

Совпадение в полном тексте источника
… The transmembrane domain of CD3ζ in this CAR design should facilitate its association with the endogenous TCR/CD3 complex, thereby enhancing CAR sensitivity ( 34 ). … 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 – 49 . 10.4049/jimmunol.0901766 20483753 35. …

Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immu